Possible pathogenic role of T helper type 9 cells and interleukin (IL)-9 in atopic dermatitis

Clinical and Experimental Immunology - Tập 175 Số 1 - Trang 25-31 - 2013
Lei Ma1, H-B Xue2, X-H Guan3, C-M Shu1, J-H Zhang1, Jianxiu Yu1
1Department of Dermatology, Binzhou Medical University Hospital, Binzhou, China
2Department of Endocrinology and Metabolism, School of Clinical Medicine, Binzhou Medical University, Binzhou, China
3State Key Department of Dermatology, No.1 Hospital of China Medical University, Shenyang, China

Tóm tắt

SummaryT helper type 9 (Th9) cells are a novel identified subset of CD4+ T helper cells, which could partly contribute to allergic inflammation, while the precise contribution of Th9 cells in atopic dermatitis (AD) remains unknown. We aimed to explore the possible role of Th9 cells in AD pathogenesis. The Th9 cell percentage, transcription factor PU.1 and cytokine interleukin (IL)-9 mRNA levels, as well as IL-9 serum concentration in peripheral circulation, were measured in AD patients, psoriasis patients and healthy controls. The Th9 cell percentage, PU.1 and IL-9 expression levels of AD patients were all increased significantly compared with the other two control groups (P < 0·01), and correlated positively with SCORing Atopic Dermatitis index, serum immunoglobulin (Ig)E and thymus- and activation-regulated chemokine (TARC) levels (P < 0·05). In simple AD patients and AD patients complicated by allergic rhinitis or asthma, there were no significant differences in the Th9 cell percentage, PU.1 and IL-9 expression levels between them. At the same time, IL-9 and vascular endothelial growth factor (VEGF) mRNA levels were detected in AD lesions and normal skin samples, which were both distinctly elevated in AD lesions, and there was a positive association between them (P < 0·01). Keratinocytes were cultured with IL-9 stimulation and the secretion of VEGF was detected. IL-9 can promote the secretion of VEGF by keratinocytes in a time- and dose-dependent manner. In conclusion, the expansion of the Th9 cell subset, up-regulation of the PU.1 transcription factor and increased secretion of the IL-9 cytokine may contribute to the pathogenesis of AD, which may be supported by the increased release of VEGF by keratinocyes after IL-9 stimulation.

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Tài liệu tham khảo

Ma, 2009, Brain-derived neurotrophic factor gene polymorphisms and serum levels in Chinese atopic dermatitis patients, J Eur Acad Dermatol Venereol, 23, 1277, 10.1111/j.1468-3083.2009.03308.x

Ma, 2010, Association analysis of filaggrin gene mutations and atopic dermatitis in Northern China, Br J Dermatol, 162, 225, 10.1111/j.1365-2133.2009.09539.x

Fukuyama, 2012, Role of regulatory T cells in the induction of atopic dermatitis by immunosuppressive chemicals, Toxicol Lett, 213, 392, 10.1016/j.toxlet.2012.07.018

Koga, 2008, Possible pathogenic role of Th17 cells for atopic dermatitis, J Invest Dermatol, 128, 2625, 10.1038/jid.2008.111

Ma, 2012, Possible role of Th17 cells and IL-17 in the pathogenesis of atopic dermatitis in northern China, J Dermatol Sci, 68, 66, 10.1016/j.jdermsci.2012.07.009

Fan, 2011, Treatment with a neutralizing anti-murine interleukin-17 antibody after the onset of coxsackievirus b3-induced viral myocarditis reduces myocardium inflammation, Virol J, 8, 17, 10.1186/1743-422X-8-17

Yuan, 2010, Th17 cells contribute to viral replication in coxsackievirus B3-induced acute viral myocarditis, J Immunol, 185, 4004, 10.4049/jimmunol.1001718

Veldhoen, 2008, Transforming growth factor-beta ‘reprograms’ the differentiation of T helper 2 cells and promotes an IL-9-producing subset, Nat Immunol, 9, 1341, 10.1038/ni.1659

Dardalhon, 2008, IL-4 inhibits TGF-beta-induced Foxp3+ T cells and, together with TGF-beta, generates IL-9+ IL-10+ Foxp3(–) effector T cells, Nat Immunol, 9, 1347, 10.1038/ni.1677

Perumal, 2011, Regulating IL9 transcription in T helper cells, Trends Immunol, 32, 146, 10.1016/j.it.2011.01.006

Chang, 2010, The transcription factor PU.1 is required for the development of IL-9-producing T cells and allergic inflammation, Nat Immunol, 11, 527, 10.1038/ni.1867

Staudt, 2010, Interferon-regulatory factor 4 is essential for the developmental program of T helper 9 cells, Immunity, 33, 192, 10.1016/j.immuni.2010.07.014

Ciprandi, 2010, Serum interleukin 9 in allergic rhinitis, Ann Allergy Asthma Immunol, 104, 180, 10.1016/j.anai.2009.11.043

Xing, 2011, Th9: a new player in asthma pathogenesis?, J Asthma, 48, 115, 10.3109/02770903.2011.554944

Rajka, 1989, Grading of severity of atopic dermatitis, Acta Derm Venereol Suppl (Stockh), 144, 13

Stadler, 1993, Severity scoring of atopic dermatitis: the SCORAD index. Consensus Report of the European Task Force on Atopic Dermatitis, Dermatology, 186, 23, 10.1159/000247298

Noelle, 2010, Cellular sources and immune functions of interleukin-9, Nat Rev Immunol, 10, 683, 10.1038/nri2848

Schmitt, 1994, IL-9 production of naive CD4+ T cells depends on IL-2, is synergistically enhanced by a combination of TGF-beta and IL-4, and is inhibited by IFN-gamma, J Immunol, 153, 3989, 10.4049/jimmunol.153.9.3989

Goswami, 2012, Gcn5 is required for PU.1-dependent IL-9 induction in Th9 cells, J Immunol, 189, 3026, 10.4049/jimmunol.1201496

Ciprandi, 2013, Serum interleukin-9 levels are associated with clinical severity in children with atopic dermatitis, Pediatr Dermatol, 30, 222, 10.1111/j.1525-1470.2012.01766.x

van Leeuwen, 1989, Molecular organization of the cytokine gene cluster, involving the human IL-3, IL-4, IL-5, and GM-CSF genes, on human chromosome 5, Blood, 73, 1142, 10.1182/blood.V73.5.1142.1142

Postma, 1995, Genetic susceptibility to asthma – bronchial hyperresponsiveness coinherited with a major gene for atopy, N Engl J Med, 333, 894, 10.1056/NEJM199510053331402

Noguchi, 1997, Evidence for linkage between asthma/atopy in childhood and chromosome 5q31-q33 in a Japanese population, Am J Respir Crit Care Med, 156, 1390, 10.1164/ajrccm.156.5.9702084

Doull, 1996, Allelic association of gene markers on chromosomes 5q and 11q with atopy and bronchial hyperresponsiveness, Am J Respir Crit Care Med, 153, 1280, 10.1164/ajrccm.153.4.8616554

Namkung, 2011, An association between IL-9 and IL-9 receptor gene polymorphisms and atopic dermatitis in a Korean population, J Dermatol Sci, 62, 16

Kakinuma, 2001, 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, 107, 535, 10.1067/mai.2001.113237

Soroosh, 2009, Th9 and allergic disease, Immunology, 127, 450, 10.1111/j.1365-2567.2009.03114.x

Chen, 2008, The progression of inflammation parallels the dermal angiogenesis in a keratin 14 IL-4-transgenic model of atopic dermatitis, Microcirculation, 15, 49, 10.1080/10739680701418416

Zhang, 2006, Increased production of vascular endothelial growth factor in the lesions of atopic dermatitis, Arch Dermatol Res, 297, 425, 10.1007/s00403-006-0641-9

Sismanopoulos, 2012, IL-9 induces VEGF secretion from human mast cells and IL-9/IL-9 receptor genes are overexpressed in atopic dermatitis, PLOS One, 7, e33271, 10.1371/journal.pone.0033271

Demoulin, 1998, Interleukin 9 and its receptor: an overview of structure and function, Int Rev Immunol, 16, 345, 10.3109/08830189809043001

Detmar, 1995, Keratinocyte-derived vascular permeability factor (vascular endothelial growth factor) is a potent mitogen for dermal microvascular endothelial cells, J Invest Dermatol, 105, 44, 10.1111/1523-1747.ep12312542

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Thông tin xuất bản

Clinical and Experimental Immunology

Tập 175 Số 1

25-31

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