Chemical-induced contact allergy: from mechanistic understanding to risk prevention

Aeby P, Python F, Goebel C (2007) Skin sensitization: understanding the in vivo situation for the development of reliable in vitro test approaches. ALTEX 24(Spec No):3–5. http://3r-training.tierversuch.ch/en/module_3r/sensitization_in-vitro/acd Agren UM, Tammi RH, Tammi MI (1997) Reactive oxygen species contribute to epidermal hyaluronan catabolism in human skin organ culture. Free Radic Biol Med 23(7):996–1001. https://doi.org/10.1016/S0891-5849(97)00098-1 Akiba H, Kehren J, Ducluzeau MT, Krasteva M, Horand F, Kaiserlian D, Kaneko F, Nicolas JF (2002) Skin inflammation during contact hypersensitivity is mediated by early recruitment of CD8 + T cytotoxic 1 cells inducing keratinocyte apoptosis. J Immunol 168(6):3079–3087. https://doi.org/10.4049/jimmunol.168.6.3079 Alase A, Wittmann M (2012) Therapeutic strategies in allergic contact dermatitis. Recent Pat Inflamm Allergy Drug Discov 6(3):210–221. https://doi.org/10.2174/187221312802652794 Alloul-Ramdhani M, Tensen CP, El Ghalbzouri A (2014) Performance of the N/TERT epidermal model for skin sensitizer identification via Nrf2-Keap1-ARE pathway activation. Toxicol In Vitro 28(5):982–989. https://doi.org/10.1016/j.tiv.2014.04.007 Aptula AO, Roberts DW, Pease CK (2007) Haptens, prohaptens and prehaptens, or electrophiles and proelectrophiles. Contact Dermat 56(1):54–56. https://doi.org/10.1111/j.1600-0536.2007.00944.x Averbeck M, Kuhn S, Bühligen J, Götte M, Simon JC, Polte T (2017) DC migration. Syndecan-1 regulates dendritic cell migration in cutaneous hypersensitivity to haptens. Exp Dermatol 26(11):1060–1067. https://doi.org/10.1111/exd.13374 Babina M, Guhl S, Artuc M, Zuberbier T (2016) IL-4 and human skin mast cells revisited: reinforcement of a pro-allergic phenotype upon prolonged exposure. Arch Dermatol Res 308(9):665–670. https://doi.org/10.1007/s00403-016-1688-x Bajorath J (2000) Molecular organization, structural features, and ligand binding characteristics of Cd44, a highly variable cell surface glycoprotein with multiple functions. Proteins 39(2):103–111. https://doi.org/10.1002/(SICI)1097-0134(20000501)39:2%3C103::AID-PROT1%3E3.0.CO;2-G Basketter DA, Kimber I (2009) Updating the skin sensitization in vitro data assessment paradigm in 2009. J Appl Toxicol 29(6):545–550. https://doi.org/10.1002/jat.1443 Basketter DA, Balikie L, Dearman RJ, Kimber I, Ryan CA, Gerberick GF, Harvey P, Evans P, White IR, Rycroft RJ (2000) Use of the local lymph node assay for the estimation of relative contact allergenic potency. Contact Dermat 42(6):344–348. https://doi.org/10.1034/j.1600-0536.2000.042006344.x Bhatia S (2016) Natural polymer drug delivery systems: nanoparticles, plants, and algae. Springer International Publishing, Cham, pp 1–32 Bhoyar N, Giri TK, Tripathi DK, Alexander AA (2012) Recent advances in novel drug delivery system through gels: review. J Pharm Allied Health Sci 2:21–39. https://doi.org/10.3923/jpahs.2012.21.39 Boukhman MP, Maibach HI (2001) Thresholds in contact sensitization: immunologic mechanisms and experimental evidence in humans—an overview. Food Chem Toxicol 39(12):1125–1134. https://doi.org/10.1016/S0278-6915(01)00062-X Bourguignon LY (2014) Matrix hyaluronan-activated Cd44 signaling promotes keratinocyte activities and improves abnormal epidermal functions. Am J Pathol 184(7):1912–1919. https://doi.org/10.1016/j.ajpath.2014.03.010 Boverhof DR, Billington R, Gollapudi BB, Hotchkiss JA, Krieger SM, Poole A, Wiescinski CM, Woolhiser MR (2008) Respiratory sensitization and allergy: current research approaches and needs. Toxicol Appl Pharmacol 226(1):1–13. https://doi.org/10.1016/j.taap.2007.10.008 Bryniarski K, Ptak W, Jayakumar A, Püllmann K, Caplan MJ, Chairoungdua A, Lu J, Adams BD, Sikora E, Nazimek K, Marquez S, Kleinstein SH, Sangwung P, Iwakiri Y, Delgato E, Redegeld F, Blokhuis BR, Wojcikowski J, Daniel AW, Groot Kormelink T, Askenase PW (2013) Antigen-specific, antibody-coated, exosome-like nanovesicles deliver suppressor T-cell microRNA-150 to effector T cells to inhibit contact sensitivity. J Allergy Clin Immunol 132(1):170–181. https://doi.org/10.1016/j.jaci.2013.04.048 Campo GM, Avenoso A, Campo S, D’Ascola A, Nastasi G, Calatroni A (2010) Small hyaluronan oligosaccharides induce inflammation by engaging both toll-like-4 and CD44 receptors in human chondrocytes. Biochem Pharmacol 80(4):480–490. https://doi.org/10.1016/j.bcp.2010.04.024 Casati S, Aschberger K, Barroso J, Casey W, Delgado I, Kim TS, Kleinstreuer N, Kojima H, Lee JK, Lowit A, Park HK, Régimbald-Krnel MJ, Strickland J, Whelan M, Yang Y, Zuang V (2018) Standardisation of defined approaches for skin sensitisation testing to support regulatory use and international adoption: position of the International Cooperation on Alternative Test Methods. Arch Toxicol 92(2):611–617. https://doi.org/10.1007/s00204-017-2097-4 Cavani A (2008) Immune regulatory mechanisms in allergic contact dermatitis and contact sensitization. Chem Immunol Allergy 94:93–100. https://doi.org/10.1159/000154934 Cavani A, De Pità O, Girolomoni G (2007) New aspects of the molecular basis of contact allergy. Curr Opin Allergy Clin Immunol 7(5):404–408. https://doi.org/10.1097/ACI.0b013e3282ef6923 Chen G, Qiu H, Prasad PN, Chen X (2014) Upconversion nanoparticles: design, nanochemistry, and applications in theranostics. Chem Rev 114:5161–5214. https://doi.org/10.1021/cr400425h Coricovac DE, Moacă EA, Pinzaru I, Cîtu C, Soica C, Mihali CV, Păcurariu C, Tutelyan VA, Tsatsakis A, Dehelean CA (2017) Biocompatible colloidal suspensions based on magnetic iron oxide nanoparticles: synthesis, characterization and Toxicological profile. Front Pharmacol 8:154. https://doi.org/10.3389/fphar.2017.00154 Corsini E, Mitjans M, Galbiati V, Lucchi L, Galli CL, Marinovich M (2009) Use of IL-18 production in a human keratinocyte cell line to discriminate contact sensitizers from irritants and low molecular weight respiratory allergens. Toxicol In Vitro 23(5):789–796. https://doi.org/10.1016/j.tiv.2009.04.005 Corsini E, Galbiati V, Nikitovic D, Tsatsakis AM (2013) Role of oxidative stress in chemical allergens induced skin cells activation. Food Chem Toxicol 61:74–81. https://doi.org/10.1016/j.fct.2013.02.038 Cottrez F, Boitel E, Ourlin JC, Peiffer JL, Fabre I, Henaoui IS, Mari B, Vallauri A, Paquet A, Barbry P, Auriault C, Aeby P, Groux H (2016) SENS-IS, a 3D reconstituted epidermis based model for quantifying chemical sensitization potency: reproducibility and predictivity results from an inter-laboratory study. Toxicol In Vitro 32:248–260. https://doi.org/10.1016/j.tiv.2016.01.007 Crosera M, Adami G, Mauro M, Bovenzi M, Baracchini E, Larese Filon F (2016) In vitro dermal penetration of nickel nanoparticles. Chemosphere 145:301–306. https://doi.org/10.1016/j.chemosphere.2015.11.076 Dhingra N, Shemer A, da Rosa JC, Rozenblit M, Fuentes-Duculan J, Gittler JK, Finney R, Czarnowicki T, Zheng X, Xu H, Estrada YD, Cardinale I, Suárez-Fariñas M, Krueger JG, Guttman-Yassky E (2014) Molecular profiling of contact dermatitis skin identifies allergen-dependent differences in immune response. J Allergy Clin Immunol 134(2):362–372. https://doi.org/10.1016/j.jaci.2014.03.009 Döge N, Hadam S, Volz P, Wolf A, Schönborn KH, Blume-Peytavi U, Alexiev U, Vogt A (2018) Identification of polystyrene nanoparticle penetration across intact skin barrier as rare event at sites of focal particle aggregations. J Biophotonics 11(4):e201700169. https://doi.org/10.1002/jbio.201700169 dos Santos GG, Reinders J, Ouwehand K, Rustemeyer T, Scheper RJ, Gibbs S (2009) Progress on the development of human in vitro dendritic cell based assays for assessment of the sensitizing potential of a compound. Toxicol Appl Pharmacol 236(3):372–382. https://doi.org/10.1016/j.taap.2009.02.004 Ebner S, Nguyen VA, Forstner M, Wang YH, Wolfram D, Liu YJ, Romani N (2007) Thymic stromal lymphopoietin converts human epidermal Langerhans cells into antigen-presenting cells that induce proallergic T cells. J Allergy Clin Immunol 119(4):982–990. https://doi.org/10.1016/j.jaci.2007.01.003 Ehling S, Roßbach K, Dunston SM, Stark H, Bäumer W (2016) Allergic inflammation is augmented via histamine H4 receptor activation: the role of natural killer cells in vitro and in vivo. J Dermatol Sci 83(2):106–115. https://doi.org/10.1016/j.jdermsci.2016.04.011 Esser PR, Wolfle U, Durr C, von Loewenich FD, Schempp CM, Freudenberg MA, Jakob T, Martin SF (2012) Contact sensitizers induce skin inflammation via ROS production and hyaluronic acid degradation. PLoS One 7(7):e41340. https://doi.org/10.1371/journal.pone.0041340 Esser PR, Kimber I, Martin SF (2014) Correlation of contact sensitizer potency with T cell frequency and TCR repertoire diversity. EXS 104:101–114. https://doi.org/10.1007/978-3-0348-0726-5_8 Ezendam J, Bokkers BGH, Bil W, Delmaar JE (2018) Skin sensitization quantitative risk assessment (QRA) based on aggregate dermal exposure to methylisothiazolinone in personal care and household cleaning products. Food Chem Toxicol 112:242–250. https://doi.org/10.1016/j.fct.2017.12.054 Freudenberg MA, Esser PR, Jakob T, Galanos C, Martin SF (2009) Innate and adaptive immune responses in contact dermatitis: analogy with infections. G Ital Dermatol Venereol 144(2):173–185 Friedmann PS, Pickard C (2014) Contact hypersensitivity: quantitative aspects, susceptibility and risk factors. EXS 104:51–71. https://doi.org/10.1007/978-3-0348-0726-5_5 Friedmann PS, Moss C, Shuster S, Simpson JS (1983) Quantitative relationship between sensitizing dose of DNCB and reactivity in normal subjects. Clin Exp Immunol 53:709–715 Frombach J, Sonnenburg A, Krapohl BD, Zuberbier T, Stahlmann R, Schreiner M (2017) A novel method to generate monocyte-derived dendritic cells during coculture with HaCaT facilitates detection of weak contact allergens in cosmetics. Arch Toxicol 91(1):339–350. https://doi.org/10.1007/s00204-016-1722-y Gaide O, Emerson RO, Jiang X, Gulati N, Nizza S, Desmarais C, Robins H, Krueger JG, Clark RA, Kupper TS (2015) Common clonal origin of central and resident memory T cells following skin immunization. Nat Med 21(6):647–653. https://doi.org/10.1038/nm.3860 Galbiati V, Corsini E (2012) The NCTC 2544 IL-18 assay for the in vitro identification of contact allergens. Curr Protoc Toxicol. https://doi.org/10.1002/0471140856.tx2008s54 Galbiati V, Carne A, Mitjans M, Galli CL, Marinovich M, Corsini E (2012) Isoeugenol destabilizes IL-8 mRNA expression in THP-1 cells through induction of the negative regulator of mRNA stability tristetraprolin. Arch Toxicol 86(2):239–248. https://doi.org/10.1007/s00204-011-0758-2 Galbiati V, Cornaghi L, Gianazza E, Potenza MA, Donetti E, Marinovich M, Corsini E (2018) In vitro assessment of silver nanoparticles immunotoxicity. Food Chem Toxicol 112:363–374. https://doi.org/10.1016/j.fct.2017.12.023 Galli SJ, Tsai M (2012) IgE and mast cells in allergic disease. Nat Med 18(5):693–704. https://doi.org/10.1038/nm.2755 Gerberick GF, Robinson MK (2000) Skin sensitization risk assessment of new products. Am J Contact Dermat 11:65–73 Gerberick GF, Sikorski EE (1998) In vitro and in vivo testing techniques for allergic contact dermatitis. Am J Contact Dermat 9(2):111–118 Gerberick GF, Vassallo JD, Foertsch LM, Price BB, Chaney JG, Lepoittevin JP (2007) Quantification of chemical peptide reactivity for screening contact allergens: a classification tree model approach. Toxicol Sci 97(2):417–427. https://doi.org/10.1093/toxsci/kfm064 Gibbs S, Corsini E, Spiekstra SW, Galbiati V, Fuchs HW, Degeorge G, Troese M, Hayden P, Deng W, Roggen E (2013) An epidermal equivalent assay for identification and ranking potency of contact sensitizers. Toxicol Appl Pharmacol 272(2):529–541. https://doi.org/10.1016/j.taap.2013.07.003 Gimenez-Rivera VA, Siebenhaar F, Zimmermann C, Siiskonen H, Metz M, Maurer M (2016) Mast cells limit the exacerbation of chronic allergic contact dermatitis in response to repeated allergen exposure. J Immunol 197(11):4240–4246. https://doi.org/10.4049/jimmunol.1600236 Girolomoni G, Gisondi P, Ottaviani C, Cavani A (2004) Immunoregulation of allergic contact dermatitis. Eur J Dermatol 31(4):264–270. https://doi.org/10.1111/j.1346-8138.2004.tb00671.x Gober MD, Gaspari AA (2008) Allergic contact dermatitis. Curr Dir Autoimmun 10:1–26. https://doi.org/10.1159/000131410 Goldberg M, Langer R, Jia X (2007) Nanostructured materials for applications in drug delivery and tissue engineering. J Biomater Sci Polym Ed 18:241–268 Gorbachev AV, Fairchild RL (2004) CD4 + T cells regulate CD8 + T cell-mediated cutaneous immune responses by restricting effector T cell development through a Fas ligand-dependent mechanism. J Immunol 172(4):2286–2295. https://doi.org/10.4049/jimmunol.172.4.2286 Guyard-Nicodème M, Gerault E, Platteel M, Peschard O, Veron W, Mondon P, Pascal S, Feuilloley MG. Development of a multiparametric in vitro model of skin sensitization (2015) J Appl Toxicol 35(1):48–58. https://doi.org/10.1002/jat.2986 He D, Wu L, Kim HK, Li H, Elmets CA, Xu H (2009) IL-17 and IFN-gamma mediate the elicitation of contact hypersensitivity responses by different mechanisms and both are required for optimal responses. J Immunol 183(2):1463–1470. https://doi.org/10.4049/jimmunol.0804108 Hirai T, Yoshioka Y, Takahashi H, Ichihashi K, Udaka A, Mori T, Nishijima N, Yoshida T, Nagano K, Kamada H, Tsunoda S, Takagi T, Ishii KJ, Nabeshi H, Yoshikawa T, Higashisaka K, Tsutsumi Y (2015) Cutaneous exposure to agglomerates of silica nanoparticles and allergen results in IgE-biased immune response and increased sensitivity to anaphylaxis in mice. Part Fibre Toxicol 12:16. https://doi.org/10.1186/s12989-015-0095-3 Hoyne GF, Lamb JR (1997) Regulation of T cell function in mucosal tolerance. Immunol Cell Biol 75:197–201. https://doi.org/10.1038/icb.1997.29 Ilves M, Palomäki J, Vippola M, Lehto M, Savolainen K, Savinko T, Alenius H (2014) Topically applied ZnO nanoparticles suppress allergen induced skin inflammation but induce vigorous IgE production in the atopic dermatitis mouse model. Part Fibre Toxicol 11:38. https://doi.org/10.1186/s12989-014-0038-4 Ishiwatari S, Suzuki T, Hitomi T, Yoshino S, Matsukuma T, Tsuji T (2007) Effects of methyl paraben on skin keratinocytes. J Appl Toxicol 27(1):1–9. https://doi.org/10.1002/jat.1176 Jäckh C, Fabian E, van Ravenzwaay B, Landsiedel R (2012) Relevance of xenobiotic enzymes in human skin in vitro models to activate pro-sensitizers. J Immunotoxicol 9(4):426–438. https://doi.org/10.3109/1547691X.2012.664578 Jawdat DM, Albert EJ, Rowden G, Haidl ID, Marshall JS (2004) IgE-mediated mast cell activation induces Langerhans cell migration in vivo. J Immunol 173(8):5275–5282. https://doi.org/10.4049/jimmunol.173.8.5275 Jin H, Kumar L, Mathias C, Zurakowski D, Oettgen H, Gorelik L, Geha R (2009) Toll-like receptor 2 is important for the T(H)1 response to cutaneous sensitization. J Allergy Clin Immunol 123(4):875–882. https://doi.org/10.1016/j.jaci.2009.02.007 e1. Karlberg AT, Bergström MA, Börje A, Luthman K, Nilsson JL (2008) Allergic contact dermatitis—formation, structural requirements, and reactivity of skin sensitizers. Chem Res Toxicol 21(1):53–69. https://doi.org/10.1021/tx7002239 Karschuk N, Tepe Y, Gerlach S, Pape W, Wenck H, Schmucker R, Wittern KP, Schepky A, Reuter H (2010) A novel in vitro method for the detection and characterization of photosensitizers. PLoS One 5(12):e15221. https://doi.org/10.1371/journal.pone.0015221 Kavasi RM, Berdiaki A, Spyridaki I, Corsini E, Tsatsakis A, Tzanakakis G, Nikitovic D (2017) HA metabolism in skin homeostasis and inflammatory disease. Food Chem Toxicol 101:128–138. https://doi.org/10.1016/j.fct.2017.01.012 Kim Y, Lee YS, Hahn JH, Choe J, Kwon HJ, Ro JY, Jeoung D (2008) Hyaluronic acid targets CD44 and inhibits FcεRI signaling involving PKCdelta, Rac1, ROS, and MAPK to exert anti-allergic effect. Mol Immunol 45(9):2537–2547. https://doi.org/10.1016/j.molimm.2008.01.008 Kimber I, Pallardy M (2014) The use of T cells in hazard characterization of chemical and drug allergens and integration in testing strategies foreword. EXS 104:1–7. https://doi.org/10.1007/978-3-0348-0726-5_1 Kimber I, Gerberick GF, Basketter DA (1999) Thresholds in contact sensitization: theoretical and practical considerations. Food Chem Toxicol 37(5):553–560. https://doi.org/10.1016/S0278-6915(99)00048-4 Kimber I, Basketter DA, Butler M, Gamer A, Garrigue JL, Gerberick GF, Newsome C, Steiling W, Vohr HW (2003) Classification of contact allergens according to potency: proposals. Food Chem Toxicol 41(12):1799–1809. https://doi.org/10.1016/S0278-6915(03)00223-0 Kindas-Mugge I, Trautinger F (1994) Increased expression of the M(R) 27,000 heat shock protein (Hsp27) in in vitro differentiated normal human keratinocytes. Cell Growth Differ 5(7):777–781 Kish DD, Gorbachev AV, Fairchild RL (2012) IL-1 receptor signaling is required at multiple stages of sensitization and elicitation of the contact hypersensitivity response. J Immunol 188(4):1761–1771. https://doi.org/10.4049/jimmunol.1100928 Klekotka PA, Yang L, Yokoyama WM (2010) Contrasting roles of the IL-1 and IL-18 receptors in MyD88-dependent contact hypersensitivity. J Investig Dermatol 130(1):184–191. https://doi.org/10.1038/jid.2009.242 Kolesaric A, Stingl G, Elbe-Bürger A (1997) MHC class I +/II − dendritic cells induce hapten-specific immune responses in vitro and in vivo. J Investig Dermatol 109(4):580–585. https://doi.org/10.1111/1523-1747.ep12337508 Koppes SA, Engebretsen KA, Agner T, Angelova-Fischer I, Berents T, Brandner J, Brans R, Clausen ML, Hummler E, Jakasa I, Jurakić-Tončic R, John SM, Khnykin D, Molin S, Holm JO, Suomela S, Thierse HJ, Kezic S, Martin SF, Thyssen JP (2017) Current knowledge on biomarkers for contact sensitization and allergic contact dermatitis. Contact Dermat 77(1):1–16. https://doi.org/10.1111/cod.12789 Krasteva M, Kehren J, Horand F, Akiba H, Choquet G, Ducluzeau MT, Tédone R, Garrigue JL, Kaiserlian D, Nicolas JF (1998) Dual role of dendritic cells in the induction and down-regulation of antigen-specific cutaneous inflammation. J Immunol 160(3):1181–1190 Kraus LF, Scheurmann N, Frenzel DF, Tasdogan A, Weiss JM (2018) 9-cis-Retinoic acid induces a distinct regulatory dendritic cell phenotype that modulates murine delayed-type allergy. Contact Dermat 78(1):41–54. https://doi.org/10.1111/cod.12868 Krieg T, Aumailley M (2011) The extracellular matrix of the dermis: flexible structures with dynamic functions. Exp Dermatol 20(8):689–695. https://doi.org/10.1111/j.1600-0625.2011.01313.x Kuskov AN, Kulikov PP, Shtilman MI, Rakitskii VN, Tsatsakis AM (2016) Amphiphilic poly-N-vynilpyrrolidone nanoparticles: cytotoxicity and acute toxicity study. Food Chem Toxicol 96:273–279. https://doi.org/10.1016/j.fct.2016.08.017 Kuskov AN, Kulikov PP, Goryachaya AV, Tzatzarakis MN, Docea AO, Velonia K, Shtilman MI, Tsatsakis AM (2017) Amphiphilic poly-N-vinylpyrrolidone nanoparticles as carriers for non-steroidal anti-inflammatory drugs: in vitro cytotoxicity and in vivo acute toxicity study. Nanomedicine 13(3):1021–1030. https://doi.org/10.1016/j.nano.2016.11.006 Lehé CL, Jacobs JJ, Elliott GR, Das PK (2003) A two-centre evaluation of the human organotypic skin explant culture model for screening contact allergens. Altern Lab Anim 31(6):553–561 Lehé CL, Jacobs JJ, Hua CM, Courtellemont P, Elliott GR, Das PK (2006) Subtoxic concentrations of allergenic haptens induce LC migration and maturation in a human organotypic skin explant culture model: a novel method for identifying potential contact allergens. Exp Dermatol 15(6):421–431. https://doi.org/10.1111/j.0906-6705.2006.00415.x Lepoittevin JP (1999) Development of structure–activity relationships (SARs) in allergic contact dermatitis. Cell Biol Toxicol 15(1):47–55. https://doi.org/10.1023/A:1007502723275 Lepoittevin JP (2006) Metabolism versus chemical transformation or pro- versus prehaptens? Contact Dermat 54(2):73–74. https://doi.org/10.1111/j.0105-1873.2006.00795.x Liaw L, Skinner MP, Raines EW, Ross R, Cheresh DA, Schwartz SM, Giachelli CM (1995) The adhesive and migratory effects of osteopontin are mediated via distinct cell surface integrins. Role of alpha v beta 3 in smooth muscle cell migration to osteopontin in vitro. J Clin Investig 95:713–724. https://doi.org/10.1172/JCI117718 Liu YJ, Soumelis V, Watanabe N, Ito T, Wang YH, de Waal Malefyt R, Omori M, Zhou B, Ziegler SF (2007) TSLP: an epithelial cell cytokine that regulates T cell differentiation by conditioning dendritic cell maturation. Annu Rev Immunol 25:193–219. https://doi.org/10.1172/JCI117718 Liu B, Escalera J, Balakrishna S, Fan L, Caceres AI, Robinson E, Sui A, McKay MC, McAlexander MA, Herrick CA, Jordt SE (2013) TRPA1 controls inflammation and pruritogen responses in allergic contact dermatitis. FASEB J 27(9):3549–3563. https://doi.org/10.1096/fj.13-229948 Loser K, Mehling A, Loeser S, Apelt J, Kuhn A, Grabbe S, Schwarz T, Penninger JM, Beissert S (2006) Epidermal RANKL controls regulatory T-cell numbers via activation of dendritic cells. Nat Med 12(12):1372–1379. https://doi.org/10.1038/nm1518 Loveless SE, Api AM, Crevel RW, Debruyne E, Gamer A, Jowsey IR, Kern P, Kimber I, Lea L, Lloyd P, Mehmood Z, Steiling W, Veenstra G, Woolhiser M, Hennes C (2010) Potency values from the local lymph node assay: application to classification, labelling and risk assessment. Regul Toxicol Pharmacol 56(1):54–66. https://doi.org/10.1016/j.jaci.2012.06.022 Luckey U, Schmidt T, Pfender N, Romer M, Lorenz N, Martin SF, Bopp T, Schmitt E, Nikolaev A, Yogev N, Waisman A, Jakob T, Steinbrink K (2012) Crosstalk of regulatory T cells and tolerogenic dendritic cells prevents contact allergy in subjects with low zone tolerance. J Allergy Clin Immunol 130(3):781–797. https://doi.org/10.1016/j.jaci.2012.06.022 Malaisse J, Bourguignon V, De Vuyst E, De Rouvroit CL, Nikkels AF, Flamion B, Poumay Y (2014) Hyaluronan metabolism in human keratinocytes and atopic dermatitis skin is driven by a balance of hyaluronan synthases 1 and 3. J Investig Dermatol 134(8):2174–2182. https://doi.org/10.1074/jbc.M115.661348 Malaisse J, Pendaries V, Hontoir F, De Glas V, Van Vlaender D, Simon M, Lambert de Rouvroit C, Poumay Y, Flamion B (2016) Hyaluronan does not regulate human epidermal keratinocyte proliferation and differentiation. J Biol Chem 291(12):6347–6358. https://doi.org/10.1074/jbc.M115.661348 Mannucci C, Casciaro M, Minciullo PL, Calapai G, Navarra M, Gangemi S (2017) Involvement of microRNAs in skin disorders: a literature review. Allergy Asthma Proc 38(1):9–15. https://doi.org/10.2500/aap.2017.38.4013 Martin SF (2012) Allergic contact dermatitis: xenoinflammation of the skin. Curr Opin Immunol 24(6):720–729. https://doi.org/10.1016/j.coi.2012.08.003 Martin SF, Dudda JC, Bachtanian E, Lembo A, Liller S, Durr C, Heimesaat MM, Bereswill S, Fejer G, Vassileva R, Jakob T, Freudenberg N, Termeer CC, Johner C, Galanos C, Freudenberg MA (2008) Toll-like receptor and IL-12 signaling control susceptibility to contact hypersensitivity. J Exp Med 205(9):2151–2162. https://doi.org/10.1084/jem.20070509 Martin SF, Esser PR, Weber FC, Jakob T, Freudenberg MA, Schmidt M, Goebeler M (2011) Mechanisms of chemical-induced innate immunity in allergic contact dermatitis. Allergy 66(9):1152–1163. https://doi.org/10.1111/j.1398-9995.2011.02652.x Martinon F, Mayor A, Tschopp J (2009) The inflammasomes: guardians of the body. Annu Rev Immunol 27:229–265. https://doi.org/10.1146/annurev.immunol.021908.132715 Maurer M, Seidel-Guyenot W, Metz M, Knop J, Steinbrink K (2003) Critical role of IL-10 in the induction of low zone tolerance to contact allergens. J Clin Investig 112(3):432–439. https://doi.org/10.1172/JCI200318106 McFadden JP, Puangpet P, Basketter DA, Dearman RJ, Kimber I (2013) Why does allergic contact dermatitis exist? Br J Dermatol 168(4):692–699. https://doi.org/10.1111/bjd.12145 McKim JM Jr, Keller DJ 3rd, Gorski JR (2012) An in vitro method for detecting chemical sensitization using human reconstructed skin models and its applicability to cosmetic, pharmaceutical and medical device safety testing. Cutan Ocul Toxicol 31(4):292–305. https://doi.org/10.3109/15569527.2012.667031 McMillan JR, Akiyama M, Shimizu H (2003) Epidermal basement membrane zone components: ultrastructural distribution and molecular interactions. J Dermatol Sci 31(3):169–177. https://doi.org/10.1016/S0923-1811(03)00045-8 Meller S, Lauerma AI, Kopp FM, Winterberg F, Anthoni M, Müller A, Gombert M, Haahtela A, Alenius H, Rieker J, Dieu-Nosjean MC, Kubitza RC, Gleichmann E, Ruzicka T, Zlotnik A, Homey B (2007) Chemokine responses distinguish chemical-induced allergic from irritant skin inflammation: memory T cells make the difference. J Allergy Clin Immunol 119(6):1470–1480. https://doi.org/10.1016/j.jaci.2006.12.654 Meyer LJ, Stern R (1994) Age-dependent changes of hyaluronan in human skin. J Investig Dermatol 102(3):385–389. https://doi.org/10.1111/1523-1747.ep12371800 Mocellin S, Panelli MC, Wang E, Nagorsen D, Marincola FM (2003) The dual role of IL-10. Trends Immunol 24(1):36–43. https://doi.org/10.1016/S1471-4906(02)00009-1 Monzon ME, Fregien N, Schmid N, Falcon NS, Campos M, Casalino-Matsuda SM, Forteza RM (2010) Reactive oxygen species and hyaluronidase 2 regulate airway epithelial hyaluronan fragmentation. J Biol Chem 285(34):26126–26134. https://doi.org/10.1074/jbc.M110.135194 Mueller MM, Fusenig NE (2004) Friends or foes—bipolar effects of the tumour stroma in cancer. Nat Rev Cancer 4(11):839–849. https://doi.org/10.1038/nrc1477 Muto J, Morioka Y, Yamasaki K, Kim M, Garcia A, Carlin AF, Varki A, Gallo RL (2014) Hyaluronan digestion controls DC migration from the skin. J Clin Investig 124(3):1309–1319. https://doi.org/10.1172/JCI67947 Mutschler J, Giménez-Arnau E, Foertsch L, Gerberick GF, Lepoittevin JP (2009) Mechanistic assessment of peptide reactivity assay to predict skin allergens with Kathon CG isothiazolinones. Toxicol In Vitro 23(3):439–446. https://doi.org/10.1016/j.tiv.2009.01.014 Nakamura N, Tamagawa-Mineoka R, Ueta M, Kinoshita S, Katoh N (2015) Toll-like receptor 3 increases allergic and irritant contact dermatitis. J Investig Dermatol 135(2):411–417. https://doi.org/10.1038/jid.2014.402 Nakao M, Sugaya M, Takahashi N, Otobe S, Nakajima R, Oka T, Kabasawa M, Suga H, Morimura S, Miyagaki T, Fujita H, Asano Y, Sato S (2016) Increased syndecan-4 expression in sera and skin of patients with atopic dermatitis. Arch Dermatol Res 308(9):655–660. https://doi.org/10.1007/s00403-016-1683-2 Nazimek K, Bryniarski K, Askenase PW (2016) Functions of exosomes and microbial extracellular vesicles in allergy and contact and delayed-type hypersensitivity. Int Arch Allergy Immunol 171(1):1–26. https://doi.org/10.1159/000449249 Neagu M, Piperigkou Z, Karamanou K, Engin AB, Docea AO, Constantin C, Negrei C, Nikitovic D, Tsatsakis A (2017) Protein bio-corona: critical issue in immune nanotoxicology. Arch Toxicol 91(3):1031–1048. https://doi.org/10.1007/s00204-016-1797-5 Neill T, Schaefer L, Iozzo RV (2015) Decoding the matrix: instructive roles of proteoglycan receptors. Biochemistry 54(30):4583–4598. https://doi.org/10.1021/acs.biochem.5b00653 Nikitovic D, Aggelidakis J, Young MF, Iozzo RV, Karamanos NK, Tzanakakis GN (2012) The biology of small leucine-rich proteoglycans in bone pathophysiology. J Biol Chem 287(41):33926–33933. https://doi.org/10.1074/jbc.R112.379602 Nikitovic D, Corsini E, Kouretas D, Tsatsakis A, Tzanakakis G (2013) ROS-major mediators of extracellular matrix remodeling during tumor progression. Food Chem Toxicol 61:178–186. https://doi.org/10.1016/j.fct.2013.06.013 Nikitovic D, Mytilinaiou M, Berdiaki A, Karamanos NK, Tzanakakis GN (2014) Heparan sulfate proteoglycans and heparin regulate melanoma cell functions. Biochim Biophys Acta 1840(8):2471–2481. https://doi.org/10.1016/j.bbagen.2014.01.031 Nikitovic D, Berdiaki A, Galbiati V, Kavasi RM, Papale A, Tsatsakis A, Tzanakakis GN, Corsini E (2015) Hyaluronan regulates chemical allergen-induced IL-18 production in human keratinocytes. Toxicol Lett 232(1):89–97. https://doi.org/10.1016/j.toxlet.2014.09.026 Noble PW (2002) Hyaluronan and its catabolic products in tissue injury and repair. Matrix Biol 21(1):25–29. https://doi.org/10.1016/S0945-053X(01)00184-6 Nosbaum A, Vocanson M, Rozieres A, Hennino A, Nicolas JF (2009) Allergic and irritant contact dermatitis. Eur J Dermatol 19(4):325–332. https://doi.org/10.1684/ejd.2009.0686 Nukada Y, Miyazawa M, Kazutoshi S, Sakaguchi H, Nishiyama N (2013) Data integration of non-animal tests for the development of a test battery to predict the skin sensitizing potential and potency of chemicals. Toxicol In Vitro 27(2):609–618. https://doi.org/10.1016/j.tiv.2012.11.006 O’Regan AW, Chupp GL, Lowry JA, Goetschkes M, Mulligan N, Berman JS (1999) Osteopontin is associated with T cells in sarcoid granulomas and has T cell adhesive and cytokine-like properties in vitro. J Immunol 162(2):1024–1031 Oakes T, Heather JM, Best K, Byng-Maddick R, Husovsky C, Ismail M, Joshi K, Maxwell G, Noursadeghi M, Riddell N, Ruehl T, Turner CT, Uddin I, Chain B (2017) Quantitative characterization of the T cell receptor repertoire of naïve and memory subsets using an integrated experimental and computational pipeline which is robust, economical and versatile. Front Immunol 8:1267. https://doi.org/10.3389/fimmu.2017.01267 OECD (2014) The adverse outcome pathway for skin sensitisation initiated by covalent binding to proteins. OECD Publishing, Paris. https://doi.org/10.1787/9789264221444-en Oesch F, Fabian E, Landsiedel R (2018) Xenobiotica-metabolizing enzymes in the skin of rat, mouse, pig, guinea pig, man, and in human skin models. Arch Toxicol 92(8):2411–2456. https://doi.org/10.1007/s00204-018-2232-x Ohno S, Drummen GP, Kuroda M (2016) Focus on extracellular vesicles: development of extracellular vesicle-based therapeutic systems. Int J Mol Sci 17(2):172. https://doi.org/10.3390/ijms17020172 Ohtani T, Memezawa A, Okuyama R, Sayo T, Sugiyama Y, Inoue S, Aiba S (2009) Increased hyaluronan production and decreased E-cadherin expression by cytokine-stimulated keratinocytes lead to spongiosis formation. J Investig Dermatol 129(6):1412–1420. https://doi.org/10.1038/jid.2008.394 Ohtsu H, Seike M (2017) Histamine and histamine receptors in allergic dermatitis. Handb Exp Pharmacol 241:333–345. https://doi.org/10.1007/164_2016_9 Pinzaru I, Coricovac D, Dehelean C, Moacă EA, Mioc M, Baderca F, Sizemore I, Brittle S, Marti D, Calina CD, Tsatsakis AM, Şoica C (2018) Stable PEG-coated silver nanoparticles—a comprehensive toxicological profile. Food Chem Toxicol 111:546–556. https://doi.org/10.1016/j.fct.2017.11.051 Piperigkou Z, Karamanou K, Engin AB, Gialeli C, Docea AO, Vynios DH, Pavão MS, Golokhvast KS, Shtilman MI, Argiris A, Shishatskaya E, Tsatsakis AM (2016) Emerging aspects of nanotoxicology in health and disease: from agriculture and food sector to cancer therapeutics. Food Chem Toxicol 91:42–57. https://doi.org/10.1016/j.fct.2016.03.003 Pistoor FH, Rambukkana A, Kroezen M, Lepoittevin JP, Bos JD, Kapsenberg ML, Ramadan Q, Ting FC (2016) In vitro micro-physiological immune-competent model of the human skin. Lab Chip 16(10):1899–1908. https://doi.org/10.1039/c6lc00229c Potter TM, Neun BW, Dobrovolskaia MA (2018) In vitro and in vivo methods for analysis of nanoparticle potential to induce delayed-type hypersensitivity reactions. Methods Mol Biol 1682:197–210. https://doi.org/10.1007/978-1-4939-7352-1_17 Pozzi A, Yurchenco PD, Iozzo RV (2017) The nature and biology of basement membranes. Matrix Biol 57–58:1–11. https://doi.org/10.1016/j.matbio.2016.12.009 Ptak W, Nazimek K, Askenase PW, Bryniarski K (2015) From mysterious supernatant entity to miRNA-150 in antigen-specific exosomes: a history of hapten-specific T suppressor factor. Arch Immunol Ther Exp (Warsz) 63(5):345–356. https://doi.org/10.1007/s00005-015-0331-4 Ramadan Q, Ting FC (2016) In vitro micro-physiological immune-competent model of the human skin. Lab Chip 16(10):1899–1908. https://doi.org/10.1039/c6lc00229c Rambukkana A, Pistoor FH, Bos JD, Kapsenberg ML, Das PK (1996) Effects of contact allergens on human Langerhans cells in skin organ culture: migration, modulation of cell surface molecules, and early expression of interleukin-1 beta protein. Lab Investig J Tech Methods Pathol 74(2):422–436 Rancan F, Gao Q, Graf C, Troppens S, Hadam S, Hackbarth S, Kembuan C, Blume-Peytavi U, Rühl E, Lademann J, Vogt A (2012) Skin penetration and cellular uptake of amorphous silica nanoparticles with variable size, surface functionalization, and colloidal stability. ACS Nano 6(8):6829–6842. https://doi.org/10.1021/nn301622h REACH (2006) Regulation (EC) No 1907/2006 of the european parliament and of the Council of 18 December 2006 concerning the registration, evaluation, authorisation and restriction of chemicals (REACH), and its guidance documents; available at: http://eurlex.europa.eu/LexUriServ/LexUriServ.do%3Furi=OJ:L:2006:396:0001:0849:EN:PDF, and at: http://guidance.echa.europa.eu/docs/guidance_document/information_requirements_en.htm Reduta T, Śniecińska M, Pawłoś A, Sulkiewicz A, Sokołowska M (2015) Serum osteopontin levels in disseminated allergic contact dermatitis. Adv Med Sci 60(2):273–276. https://doi.org/10.1016/j.advms.2015.05.001 Rees JL, Friedmann PS, Matthews JN (1990) The influence of area of application on sensitization by dinitrochlorobenzene. Br J Dermatol 122:29–31. https://doi.org/10.1111/j.1365-2133.1990.tb08236.x Robinson NA, LaCelle PT, Eckert RL (1996) Involucrin is a covalently crosslinked constituent of highly purified epidermal corneocytes: evidence for a common pattern of involucrin crosslinking in vivo and in vitro. J Investig Dermatol 107(1):101–107 Robinson MK, Gerberick GF, Ryan CA, McNamee P, White I, Basketter DA (2000) The importance of exposure in the assessment of skin sensitization risk. Contact Dermat 42:251–259. https://doi.org/10.1034/j.1600-0536.2000.042005251.x Rustemeyer T, Preuss M, von Blomberg BM, Das PK, Scheper RJ (2003) Comparison of two in vitro dendritic cell maturation models for screening contact sensitizers using a panel of methacrylates. Exp Dermatol 12(5):682–691. https://doi.org/10.1034/j.1600-0625.2003.00077.x Saint-Mezard P, Berard F, Dubois B, Kaiserlian D, Nicolas JF (2004) The role of CD4 + and CD8 + T cells in contact hypersensitivity and allergic contact dermatitis. Eur J Dermatol 14(3):131–138 Sakaguchi H, Ashikaga T, Miyazawa M, Yoshida Y, Ito Y, Yoneyama K, Hirota M, Itagaki H, Toyoda H, Suzuki H (2006) Development of an in vitro skin sensitization test using human cell lines; human Cell Line Activation Test (h-CLAT). II. An inter-laboratory study of the h-CLAT. Toxicol In Vitro 20(5):774–784. https://doi.org/10.1016/j.tiv.2005.10.014 Salamon P, Shefler I, Hershko AY, Mekori YA (2016) The involvement of protein kinase D in T cell-induced mast cell activation. Int Arch Allergy Immunol 171(3–4):203–208. https://doi.org/10.1159/000452625 Sayo T, Sugiyama Y, Takahashi Y, Ozawa N, Sakai S, Ishikawa O, Tamura M, Inoue S (2002) Hyaluronan synthase 3 regulates hyaluronan synthesis in cultured human keratinocytes. J Investig Dermatol 118(1):43–48. https://doi.org/10.1046/j.0022-202x.2001.01613.x Schaefer L (2014) Complexity of danger: the diverse nature of damage-associated molecular patterns. J Biol Chem 289(51):35237–35245. https://doi.org/10.1074/jbc.R114.619304 Seidel-Guyenot W, Alt R, Perschon S, Knop J, Steinbrink K (2004) B cells are not required for T cell priming in low zone tolerance to contact allergens and contact hypersensitivity. Eur J Immunol 34(11):3082–3090. https://doi.org/10.1002/eji.200425402 Shao M, Hussain Z, Thu HE, Khan S, Katas H, Ahmed TA, Tripathy M, Leng J, Qin HL, Bukhari SNA (2016) Drug nanocarrier, the future of atopic diseases: advanced drug delivery systems and smart management of disease. Colloids Surf B Biointerfaces 147:475–491. https://doi.org/10.1016/j.colsurfb.2016.08.027 Sher I, Zisman-Rozen S, Eliahu L, Whitelock JM, Maas-Szabowski N, Yamada Y, Breitkreutz D, Fusenig NE, Arikawa-Hirasawa E, Iozzo RV, Bergman R, Ron D (2006) Targeting perlecan in human keratinocytes reveals novel roles for perlecan in epidermal formation. J Biol Chem 281(8):5178–5187. https://doi.org/10.1074/jbc.M509500200 Shin JW, Choi YJ, Choi HR, Na JI, Kim KH, Park IA, Lee HS, Park KC (2015) Defective basement membrane in atopic dermatitis and possible role of IL-13. Eur Acad Dermatol Venereol 29(10):2060–2062. https://doi.org/10.1111/jdv.12596 Sloane JA, Blitz D, Margolin Z, Vartanian T (2010) A clear and present danger: endogenous ligands of Toll-like receptors. Neuromol Med 12(2):149–163. https://doi.org/10.1007/s12017-009-8094-x Smulders S, Golanski L, Smolders E, Vanoirbeek J, Hoet PH (2015) Nano-TiO2 modulates the dermal sensitization potency of dinitrochlorobenzene after topical exposure. Br J Dermatol 172(2):392–399. https://doi.org/10.1111/bjd.13295 Soumelis V, Reche PA, Kanzler H, Yuan W, Edward G, Homey B, Gilliet M, Ho S, Antonenko S, Lauerma A, Smith K, Gorman D, Zurawski S, Abrams J, Menon S, McClanahan T, de Waal-Malefyt Rd R, Bazan F, Kastelein RA, Liu YJ (2002) Human epithelial cells trigger dendritic cell mediated allergic inflammation by producing TSLP. Nat Immunol 3(7):673–680. https://doi.org/10.1038/ni805 Steinbrink K, Sorg C, Macher E (1996) Low zone tolerance to contact allergens in mice: a functional role for CD8 + T helper type 2 cells. J Exp Med 183(3):759–768. https://doi.org/10.1084/jem.183.3.759 Stern R, Maibach HI (2008) Hyaluronan in skin: aspects of aging and its pharmacologic modulation. Clin Dermatol 26(2):106–122. https://doi.org/10.1016/j.clindermatol.2007.09.013 Stern R, Asari AA, Sugahara KN (2006) Hyaluronan fragments: an information-rich system. Eur J Cell Biol 85(8):699–715. https://doi.org/10.1016/j.ejcb.2006.05.009 Stratum corneum DH, Igyártó BZ, Gaspari AA (2012) Early immune events in the induction of allergic contact dermatitis. Nat Rev Immunol 12(2):114–124. https://doi.org/10.1038/nri3150 Strickland J, Zang Q, Kleinstreuer N, Paris M, Lehmann DM, Choksi N, Matheson J, Jacobs A, Lowit A, Allen D, Casey W (2016) Integrated decision strategies for skin sensitization hazard. J Appl Toxicol 36(9):1150–1162. https://doi.org/10.1002/jat.3281 Strickland J, Zang Q, Kleinstreuer N, Paris M, Lehmann DM, Choksi N, Matheson J, Jacobs A, Lowit A, Allen D, Casey W (2018) Integrated decision strategies for skin sensitization hazard. J Appl Toxicol 38(3):432. https://doi.org/10.1002/jat.3572 Taylor KR, Yamasaki K, Radek KA, Di Nardo A, Goodarzi H, Golenbock D, Beutler B, Gallo RL (2007) Recognition of hyaluronan released in sterile injury involves a unique receptor complex dependent on Toll-like receptor 4, CD44, and MD-2. J Biol Chem 282(25):18265–18275. https://doi.org/10.1074/jbc.M606352200 Teunis M, Corsini E, Smits M, Madsen CB, Eltze T, Ezendam J, Galbiati V, Gremmer E, Krul C, Landin A, Landsiedel R, Pieters R, Rasmussen TF, Reinders J, Roggen E, Spiekstra S, Gibbs S (2013) Transfer of a two-tiered keratinocyte assay: IL-18 production by NCTC2544 to determine the skin sensitizing capacity and epidermal equivalent assay to determine sensitizer potency. Toxicol In Vitro 27(3):1135–1150. https://doi.org/10.1016/j.tiv.2012.06.004 Toebak MJ, Gibbs S, Bruynzeel DP, Scheper RJ, Rustemeyer T (2009) Dendritic cells: biology of the skin. Contact Dermat 60(1):2–20. https://doi.org/10.1111/j.1600-0536.2008.01443.x Try C, Moulari B, Béduneau A, Fantini O, Pin D, Pellequer Y, Lamprecht A (2016) Size dependent skin penetration of nanoparticles in murine and porcine dermatitis models. Eur J Pharm Biopharm 100:101–108. https://doi.org/10.1016/j.ejpb.2016.01.002 Tsuji RF, Szczepanik M, Kawikova I, Paliwal V, Campos RA, Itakura A, Akahira-Azuma M, Baumgarth N, Herzenberg LA, Askenase PW (2002) B cell-dependent T cell responses: IgM antibodies are required to elicit contact sensitivity. J Exp Med 196(10):1277–1290. https://doi.org/10.1084/jem.20020649 Tuschl H, Kovac R (2001) Langerhans cells and immature dendritic cells as model systems for screening of skin sensitizers. Toxicol In Vitro 15(4–5):327–331. https://doi.org/10.1016/S0887-2333(01)00030-3 Tzellos TG, Sinopidis X, Kyrgidis A, Vahtsevanos K, Triaridis S, Printza A, Klagas I, Karakiulakis G, Papakonstantinou E (2011) Differential hyaluronan homeostasis and expression of proteoglycans in juvenile and adult human skin. J Dermatol Sci 61(1):69–72. https://doi.org/10.1016/j.jdermsci.2010.10.010 Valadi H, Ekström K, Bossios A, Sjöstrand M, Lee JJ, Lötvall JO (2007) Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat Cell Biol 9(6):654–659. https://doi.org/10.1038/ncb1596 Vandebriel RJ, Van Och FM, van Loveren H (2005) In vitro assessment of sensitizing activity of low molecular weight compounds. Toxicol Appl Pharmacol 207(2 Suppl):142–148. https://doi.org/10.1016/j.taap.2005.01.054 Vennegaard MT, Bonefeld CM, Hagedorn PH, Bangsgaard N, Løvendorf MB, Odum N, Woetmann A, Geisler C, Skov L (2012) Allergic contact dermatitis induces upregulation of identical microRNAs in humans and mice. Contact Dermat 67(5):298–305. https://doi.org/10.1111/j.1600-0536.2012.02083.x Vocanson M, Hennino A, Rozières A, Poyet G, Nicolas JF (2009) Effector and regulatory mechanisms in allergic contact dermatitis. Allergy 64(12):1699–1714. https://doi.org/10.1111/j.1398-9995.2009.02082.x von Blomberg-vander Flier BM, Scheper RJ (1990) In vitro tests with sensitized lymphocytes—relevance for predictive allergenicity testing. Toxicol In Vitro. 4(4–5):246–251 Wanner R, Sonnenburg A, Quatchadze M, Schreiner M, Peiser M, Zuberbier T, Stahlmann R (2010) Classification of sensitizing and irritative potential in a combined in-vitro assay. Toxicol Appl Pharmacol 245(2):211–218. https://doi.org/10.1016/j.taap.2010.02.019 Weber FC, Németh T, Csepregi JZ, Dudeck A, Roers A, Ozsvári B, Oswald E, Puskás LG, Jakob T, Mócsai A, Martin SF (2015) Neutrophils are required for both the sensitization and elicitation phase of contact hypersensitivity. J Exp Med 212(1):15–22. https://doi.org/10.1084/jem.20130062 Weigel PH, Hascall VC, Tammi M (1997) Hyaluronan synthases. J Biol Chem 272(22):13997–14000. https://doi.org/10.1074/jbc.272.22.13997 Weiss JM, Renkl AC, Maier CS, Kimmig M, Liaw L, Ahrens T, Kon S, Maeda M, Hotta H, Uede T, Simon (2001) Osteopontin is involved in the initiation of cutaneous contact hypersensitivity by inducing Langerhans and dendritic cell migration to lymph nodes. J Exp Med 194(9):1219–1229. https://doi.org/10.1084/jem.194.9.1219 Weltzien HU, Moulon C, Martin S, Padovan E, Hartmann U, Kohler J (1996) T cell immune responses to haptens. Structural models for allergic and autoimmune reactions. Toxicology 107(2):141–151. https://doi.org/10.1016/0300-483X(95)03253-C White SJ, Friedmann PS, Moss C, Simpson JM (1986) The effect of altering area of application and dose per unit area on sensitization to DNCB. Br J Dermatol 115:663–668. https://doi.org/10.1111/j.1365-2133.1986.tb06646.x Xu H, DiIulio NA, Fairchild RL (1996) T cell populations primed by hapten sensitization in contact sensitivity are distinguished by polarized patterns of cytokine production: interferon gamma-producing (Tc1) effector CD8 + T cells and interleukin (IL) 4/IL-10-producing (Th2) negative regulatory CD4 + T cells. J Exp Med 183:1001–1012. https://doi.org/10.1084/jem.183.3.1001 Yamada Y, Itano N, Hata K, Ueda M, Kimata K (2004) Differential regulation by IL-1beta and EGF of expression of three different hyaluronan synthases in oral mucosal epithelial cells and fibroblasts and dermal fibroblasts: quantitative analysis using real-time RT-PCR. J Investig Dermatol 122(3):631–639. https://doi.org/10.1111/j.0022-202X.2004.22332.x Yurchenco PD (2011) Basement membranes: cell scaffoldings and signaling platforms. Cold Spring Harb Perspect Biol 3(2):a004911. https://doi.org/10.1101/cshperspect.a004911 Zang Q, Paris M, Lehmann DM, Bell S, Kleinstreuer N, Allen D, Matheson J, Jacobs A, Casey W, Strickland J (2017) Prediction of skin sensitization potency using machine learning approaches. J Appl Toxicol 37(7):792–805. https://doi.org/10.1002/jat.3424 Zmolik JM, Mummert MEJ (2005) Pep-1 as a novel probe for the in situ detection of hyaluronan. Histochem Cytochem 53(6):745–751. https://doi.org/10.1369/jhc.4A6491.2005 Zoeller JJ, Whitelock JM, Iozzo RV (2009) Perlecan regulates developmental angiogenesis by modulating the VEGF-VEGFR2 axis. Matrix Biol 28(5):284–291. https://doi.org/10.1016/j.matbio.2009.04.010 Zug KA, Warshaw EM, Fowler JF Jr, Maibach HI, Belsito DL, Pratt MD et al (2009) Patch-test results of the North American Contact Dermatitis Group 2005–2006. Dermatitis 20:149–160. https://doi.org/10.2310/6620.2009.08097