Immune dysregulation in atopic dermatitis

Homey B, Steinhoff M, Ruzicka T, Leung DYM: Cytokines and chemokines orchestrate atopic skin inflammation. J Allergy Clin Immunol 2006, 118:178–189. An excellent up-to-date review of mechanisms of atopic skin inflammation. Spergel JM, Mizoguchi E, Brewer JP, et al.: Epicutaneous sensitization with protein antigen induces localized allergic dermatitis and hyperresponsiveness to methacholine after single exposure to aerosolized antigen in mice. J Clin Invest 1998, 101:1614–1622. Novak N, Kruse S, Kraft S, et al.: Dichotomic nature of atopic dermatitis reflected by combined analysis of monocyte immunophenotyping and single nucleotide polymorphisms of the interleukin-4/interleukin-13 receptor gene: the dichotomy of extrinsic and intrinsic atopic dermatitis. J Invest Dermatol 2002, 119:870–875. Seki Y, Inoue H, Nagata N, et al.: SOCS-3 regulates onset and maintenance of T(H)2-mediated allergic responses. Nat Med 2003, 9:1047–1054. 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Herrick CA, Xu L, McKenzie AN, et al.: IL-13 is necessary, not simply sufficient, for epicutaneously induced Th2 responses to soluble protein antigen. J Immunol 2003, 170:2488–2495. This study illustrates the essential and independent role of IL-13 in Th2 responses. Purwar R, Werfel T, Wittmann M: IL-13-stimulated human keratinocytes preferentially attract CD4(+)CCR4(+) T cells: possible role in atopic dermatitis. J Invest Dermatol 2006, 126:1043–1051. Reich K, Hugo S, Middel P, et al.: Evidence for a role of Langerhans cell-derived IL-16 in atopic dermatitis. J Allergy Clin Immunol 2002, 109:681–687. Kakinuma T, Nakamura K, Wakugawa M, et al.: Thymus and activation-regulated chemokine in atopic dermatitis: Serum thymus and activation-regulated chemokine level is closely related with disease activity. J Allergy Clin Immunol 2001, 107:535–541. 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Klunker S, Trautmann A, Akdis M, et al.: A second step of chemotaxis after transendothelial migration: keratinocytes undergoing apoptosis release IFN-gamma-inducible protein 10, monokine induced by IFN-gamma, and IFN-gammainducible alpha-chemoattractant for T cell chemotaxis toward epidermis in atopic dermatitis. J Immunol 2003, 171:1078–1084. Echigo T, Hasegawa M, Shimada Y, et al.: Expression of fractalkine and its receptor, CX3CR1, in atopic dermatitis: possible contribution to skin inflammation. J Allergy Clin Immunol 2004, 113:940–948. Thepen T, Langeveld-Wildschut EG, Bihari IC, et al.: Biphasic response against aeroallergen in atopic dermatitis showing a switch from an initial TH2 response to a TH1 response in situ: an immunocytochemical study. J Allergy Clin Immunol 1996, 97:828–837. Trautmann A, Akdis M, Kleemann D, et al.: T cell-mediated Fas-induced keratinocyte apoptosis plays a key pathogenetic role in eczematous dermatitis. J Clin Invest 2000, 106:25–35. Savinko T, Lauerma A, Lehtimaki S, et al.: Topical superantigen exposure induces epidermal accumulation of CD8+ T cells, a mixed Th1/Th2-type dermatitis and vigorous production of IgE antibodies in the murine model of atopic dermatitis. J Immunol 2005, 175:8320–8326. Gombert M, Dieu-Nosjean MC, Winterberg F, et al.: CCL1-CCR8 interactions: an axis mediating the recruitment of T cells and Langerhans-type dendritic cells to sites of atopic skin inflammation. J Immunol 2005, 174:5082–5091. Chatila TA: Role of regulatory T cells in human diseases. J Allergy Clin Immunol 2005, 116:949–959. Lin W, Truong N, Grossman WJ, et al.: Allergic dysregulation and hyperimmunoglobulinemia E in Foxp3 mutant mice. J Allergy Clin Immunol 2005, 116:1106–1115. Verhagen J, Akdis M, Traidl-Hoffmann C, et al.: Absence of T-regulatory cell expression and function in atopic dermatitis skin. J Allergy Clin Immunol 2006, 117:176–183. T-regulatory cells are important in regulating immune responses. This paper provides a novel mechanism for the dysregulated cutaneous inflammation in AD. Goleva E, Cardona ID, Ou LS, Leung DY: Factors that regulate naturally occurring T regulatory cell-mediated suppression. J Allergy Clin Immunol 2005, 116:1094–1100. Novak N, Valenta R, Bohle B, et al.: FcepsilonRI engagement of Langerhans cell-like dendritic cells and inflammatory dendritic epidermal cell-like dendritic cells induces chemotactic signals and different T-cell phenotypes in vitro. J Allergy Clin Immunol 2004, 113:949–957. Dendritic cells are crucial in the initiation of immune responses. This paper shows the contribution of different dendritic cell subtypes in Th2- and Th1-mediated inflammation of atopic dermatitis lesions. Kerschenlohr K, Decard S, Przybilla B, Wollenberg A: Atopy patch test reactions show a rapid influx of inflammatory dendritic epidermal cells in patients with extrinsic atopic dermatitis and patients with intrinsic atopic dermatitis. J Allergy Clin Immunol 2003, 111:869–874. Novak N, Allam JP, Hagemann T, et al.: Characterization of FcepsilonRI-bearing CD123 blood dendritic cell antigen-2 plasmacytoid dendritic cells in atopic dermatitis. J Allergy Clin Immunol 2004, 114:364–370. Wollenberg A, Wagner M, Gunther S, et al.: Plasmacytoid dendritic cells: a new cutaneous dendritic cell subset with distinct role in inflammatory skin diseases. J Invest Dermatol 2002, 119:1096–1102. Ong PY, Ohtake T, Brandt C, et al.: Endogenous antimicrobial peptides and skin infections in atopic dermatitis. N Engl J Med 2002, 347:1151–1160. Howell MD, Novak N, Bieber T, et al.: Interleukin-10 downregulates antimicrobial peptide expression in atopic dermatitis. J Invest Dermatol 2005, 125:738–745. This paper shows a novel mechanism for the decreased expression of antimicrobial peptides in atopic dermatitis lesions. Howell MD, Wollenberg A, Gallo RL, et al.: Cathelicidin deficiency predisposes to eczema herpeticum. J Allergy Clin Immunol 2006, 117:836–841. Howell MD, Gallo RL, Boguniewicz M, et al.: Cytokine milieu of atopic dermatitis skin subverts the innate immune response to vaccinia virus. Immunity 2006, 24:341–348. Soumelis V, Reche PA, Kanzler H, et al.: Human epithelial cells trigger dendritic cell mediated allergic inflammation by producing TSLP. Nat Immunol 2002, 3:673–680. Pastore S, Fanales-Belasio E, Albanesi C, et al.: Granulocyte macrophage colony-stimulating factor is overproduced by keratinocytes in atopic dermatitis. Implications for sustained dendritic cell activation in the skin. J Clin Invest 1997, 99:3009–3017. Cork MK, Robinson DA, Vasilopoulos Y, et al.: New perspectives on epidermal barrier dysfunction in atopic dermatitis: gene-environment interactions. J Allergy Clin Immunol 2006, In press. Jensen JM, Folster-Holst R, Baranowsky A, et al.: Impaired sphingomyelinase activity and epidermal differentiation in atopic dermatitis. J Invest Dermatol 2004, 122:1423–1431. Larsen FS, Holm NV, Henningsen K: Atopic dermatitis. A genetic-epidemiologic study in a population-based twin sample. J Am Acad Dermatol 1986, 15:487–494. Morar N, Willis-Owen SA, Moffatt MF, Cookson WO: The genetics of atopic dermatitis. J Allergy Clin Immunol 2006, In press. An outstanding update on the genetics of AD. Palmer CN, Irvine AD, Terron-Kwiatkowski A, et al.: Common loss-of-function variants of the epidermal barrier protein filaggrin are a major predisposing factor for atopic dermatitis. Nat Genet 2006, 38:441–446. Mothes N, Niggemann B, Jenneck C, et al.: The cradle of IgE autoreactivity in atopic eczema lies in early infancy. J Allergy Clin Immunol 2005, 116:706–709. Werfel T, Breuer K, Rueff F, et al.: Usefulness of specific immunotherapy in patients with atopic dermatitis and allergic sensitization to house dust mites: a multi-centre, randomized, dose-response study. Allergy 2006, 61:202–205. Pivarcsi A, Homey B: Chemokine networks in atopic dermatitis: traffic signals of disease. Curr Allergy Asthma Rep 2005, 5:284–290. Sonkoly E, Muller A, Lauerma AI, et al.: IL-31: a new link between T cells and pruritus in atopic skin inflammation. J Allergy Clin Immunol 2006, 117:411–417. This study illustrates how staphylococcal superantigen upregulates the expression of IL-31, a newly-described Th2 cytokine that induces pruritus in atopic dermatitis skin. Bilsborough J, Leung DY, Maurer M, et al.: IL-31 is associated with cutaneous lymphocyte antigen-positive skin homing T cells in patients with atopic dermatitis. J Allergy Clin Immunol 2006, 117:418–425. This study shows that IL-31 is associated with CLA+ T cells and is overexpressed in atopic dermatitis lesions. Schmid-Grendelmeier P, Fluckiger S, Disch R, et al.: IgE-mediated and T cell-mediated autoimmunity against manganese superoxide dismutase in atopic dermatitis. J Allergy Clin Immunol 2005, 115:1068–1075. An important study illustrating how Malassezia may contribute to autoimmune reactions in atopic skin. Fonacier L, Spergel J, Charlesworth EN, et al.: Report of the Topical Calcineurin Inhibitor Task Force of the American College of Allergy, Asthma and Immunology and the American Academy of Allergy, Asthma and Immunology. J Allergy Clin Immunol 2005, 115:1249–1253. An evaluation of the safety of topical calcineurin inhibitors. Leung DY, Boguniewicz M, Howell MD, et al.: New insights into atopic dermatitis. J Clin Invest 2004, 113:651–657.