Early pediatric atopic dermatitis shows only a cutaneous lymphocyte antigen (CLA) 1 TH2/TH1 cell imbalance, whereas adults acquire CLA1+ TH22/TC22 cell subsets

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY

卷:136

Article

Czarnowicki, Tali¹  Esaki, Hitokazu^1,3  Gonzalez, Juana²  Malajian, Dana^1,6  Shemer, Avner⁹  Noda, Shinji¹  Talasila, Sreya^7,8  Berry, Adam^7,8  Gray, Jayla^7,8  Becker, Lauren^7,8  Estrada, Yeriel³  Xu, Hui³  Zheng, Xiuzhong¹  Suarez-Farinas, Mayte^3,4,5  Krueger, James G.¹  Paller, Amy S.^7,8  Guttman-Yassky, Emma^1,3 

[1] Rockefeller Univ, Invest Dermatol Lab, New York, NY 10021 USA

[2] Rockefeller Univ, Translat Technol Core Lab, New York, NY 10021 USA

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

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

[5] Icahn Sch Med Mt Sinai, Icahn Inst Genom & Multiscale Biol, New York, NY 10029 USA

[6] Columbia Univ Coll Phys & Surg, New York, NY 10032 USA

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

[8] Northwestern Univ, Dept Pediat, Feinberg Sch Med, Chicago, IL 60611 USA

[9] Tel Hashomer Hosp, Dept Dermatol, Tel Aviv, Israel

关键词: Atopic dermatitis;    T cell;    cutaneous lymphocyte antigen;    IL-13;    IL-22;    IFN-gamma;    inducible costimulator;    CD69;    HLA-DR;   

DOI  :  10.1016/j.jaci.2015.05.049

来源: Elsevier

【 摘 要 】

Background: Identifying differences and similarities between cutaneous lymphocyte antigen (CLA)(+) polarized T-cell subsets in children versus adults with atopic dermatitis (AD) is critical for directing new treatments toward children. Objective: We sought to compare activation markers and frequencies of skin-homing (CLA(+)) versus systemic (CLA(-)) polar'' CD4 and CD8 T-cell subsets in patients with early pediatric AD, adults with AD, and control subjects. Methods: Flow cytometry was used to measure CD69/inducible costimulator/HLA-DR frequency in memory cell subsets, as well as IFN-gamma, IL-13, IL-9, IL-17, and IL-22 cytokines, defining T(H)1/cytotoxic T(T-C) 1, T(H)2/T(C)2, TH9/T(C)9, T(H)17/T(C)17, and T(H)22/T(C)22 populations in CD4 and CD8 cells, respectively. We compared peripheral blood from 19 children less than 5 years old and 42 adults with well-characterized moderate-to-severe AD, as well as age-matched control subjects (17 children and 25 adults). Results: Selective inducible costimulator activation (P <. 001) was seen in children. CLA(+)T(H)2 T cells were markedly expanded in both children and adults with AD compared with those in control subjects, but decreases in CLA(+)T(H)1 T-cell numbers were greater in children with AD (17% vs 7.4%, P = .007). Unlike in adults, no imbalances were detected in CLA(-) T cells from pediatric patients with AD nor were there altered frequencies of T(H)22 T cells within the CLA(+) or CLA(-) compartments. adults with AD hAD increased frequencies of IL-22-producing CD4 and CD8 T cells within the skin-homing population, compared with controls (9.5% vs 4.5% and 8.6% vs 2.4%, respectively; P <. 001), as well as increased HLA-DR activation (P < .01). Conclusions: These data suggest that T(H)2 activation within skin-homing T cells might drive AD in children and that reduced counterregulation by T(H)1 T cells might contribute to excess T(H)2 activation. T(H)22 spreading'' of AD is not seen in young children and might be influenced by immune development, disease chronicity, or recurrent skin infections.

【 授权许可】

Free