Early-onset pediatric atopic dermatitis is TH2 but also TH17 polarized in skin

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY

卷:138

Article

Esaki, Hitokazu^1,2,4  Brunner, Patrick M.⁴  Renert-Yuval, Yael^1,2  Czarnowicki, Tali⁴  Thy Huynh⁵  Tran, Gary⁵  Lyon, Sarah⁵  Rodriguez, Giselle⁵  Immaneni, Supriya⁵  Johnson, Donald B.⁶  Bauer, Bruce⁶  Fuentes-Duculan, Judilyn⁴  Zheng, Xiuzhong⁴  Peng, Xiangyu^1,2  Estrada, Yeriel D.^1,2  Xu, Hui^1,2  Strong, Christina de Guzman⁷  Suarez-Farinas, Mayte^1,2,3,4,8  Krueger, James G.⁴  Paller, Amy S.⁵  Guttman-Yassky, Emma^1,2,4 

[1] Icahn Sch Med Mt Sinai, Dept Dermatol, New York, NY 10029 USA

[2] Icahn Sch Med Mt Sinai, Lab Inflammatory Skin Dis, New York, NY 10029 USA

[3] Icahn Sch Med Mt Sinai, Dept Populat Hlth Sci & Policy, New York, NY 10029 USA

[4] Rockefeller Univ, Lab Invest Dermatol, 1230 York Ave, New York, NY 10021 USA

[5] Northwestern Univ, Feinberg Sch Med, Dept Dermatol, Chicago, IL 60611 USA

[6] Univ Chicago, Pritzker Sch Med, NorthShore Univ HealthSyst, Northbrook, IL USA

[7] Washington Univ, Div Biol & Biomed Sci, St Louis, MO 63130 USA

[8] Icahn Inst Genom & Multiscale Biol, Dept Genet & Genom Sci, New York, NY USA

关键词: Atopic dermatitis;    pediatric;    adult;    skin;    T(H)2;    T(H)9;    T(H)17;    IL-17;    IL-19;    antimicrobials;   

DOI  :  10.1016/j.jaci.2016.07.013

来源: Elsevier

【 摘 要 】

Background: Atopic dermatitis (AD) affects 15% to 25% of children and 4% to 7% of adults. Paradigm-shifting discoveries about AD have been based on adult biomarkers, reflecting decades of disease activity, although 85% of cases begin by 5 years. Blood phenotyping shows only T(H)2 skewing in patients with early-onset pediatric AD, but alterations in early pediatric skin lesions are unknown, limiting advancement of targeted therapies. Objective: We sought to characterize the early pediatric AD skin phenotype and its differences from pediatric control subjects and adults with AD. Methods: Using immunohistochemistry and quantitative real-time PCR, we assessed biopsy specimens from 19 children with AD younger than 5 years within 6 months of disease onset in comparison with adults with AD or psoriasis and pediatric and adult control subjects. Results: In lesional skin children showed comparable or greater epidermal hyperplasia (thickness and keratin 16) and cellular infiltration (CD3(+), CD11c(+), and Fc epsilon RI+) than adults with AD. Similar to adults, strong activation of the T(H)2 (IL-13, IL-31, and CCL17) and T(H)22 (IL-22 and S100As) axes and some T(H)1 skewing (IFN-gamma and CXCL10) were present. Children showed significantly higher induction of T(H)17-related cytokines and antimicrobials (IL-17A, IL-19, CCL20, LL37, and peptidase inhibitor 3/elafin), T(H)9/IL-9, IL-33, and innate markers (IL-8) than adults (P < .02). Despite the characteristic downregulation in adult patients with AD, filaggrin expression was similar in children with AD and healthy children. Nonlesional skin in pediatric patients with AD showed higher levels of inflammation (particularly IL-17A and the related molecules IL-19 and LL37) and epidermal proliferation (keratin 16 and S100As) markers (P <.001). Conclusion: The skin phenotype of new-onset pediatric AD is substantially different from that of adult AD. Although excess T(H)2 activation characterizes both, T(H)9 and T(H)17 are highly activated at disease initiation. Increases in IL-19 levels might link T(H)2 and T(H)17 activation.

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