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Severe atopic dermatitis is characterized by selective expansion of circulating TH 2/TC 2 and TH 22/TC 22, but not TH 17/TC 17, cells within the skin-homing T-cell population

Background Past studies of blood T-cell phenotyping in patients with atopic dermatitis (AD) have provided controversial results and were mostly performed before the identification of TH 9, TH 17, and TH 22 T-cell populations in human subjects. Objective We sought to quantify TH 1, TH 2, TH 9, TH 17,...

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Published in:Journal of allergy and clinical immunology 2015, Vol.136 (1), p.104-115.e7
Main Authors: Czarnowicki, Tali, MD, Gonzalez, Juana, PhD, Shemer, Avner, MD, Malajian, Dana, BA, Xu, Hui, MSc, Zheng, Xiuzhong, MSc, Khattri, Saakshi, MD, Gilleaudeau, Patricia, NP, Sullivan-Whalen, Mary, NP, Suárez-Fariñas, Mayte, PhD, Krueger, James G., MD, PhD, Guttman-Yassky, Emma, MD, PhD
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Language:English
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Summary:Background Past studies of blood T-cell phenotyping in patients with atopic dermatitis (AD) have provided controversial results and were mostly performed before the identification of TH 9, TH 17, and TH 22 T-cell populations in human subjects. Objective We sought to quantify TH 1, TH 2, TH 9, TH 17, and TH 22 T-cell populations and corresponding CD8+ T-cell subsets in both cutaneous lymphocyte antigen (CLA)–positive and CLA− T-cell subsets in patients with AD and control subjects. Methods We studied 42 adults with severe AD (mean SCORAD score, 65) and 25 healthy subjects using an 11-color flow cytometric antibody panel. Frequencies of IFN-γ–, IL-22–, IL-13–, IL-17–, and IL-9–producing CD4+ and CD8+ T cells were compared in CLA− and CLA+ populations. Results We measured increased TH 2/TC 2/IL-13+ and TH 22/TC 22/IL-22+ populations ( P  < .1) in patients with severe AD versus control subjects, with significant differences in CLA+ T-cell numbers ( P  < .01). A significantly lower frequency of CLA+ IFN-γ–producing cells was observed in patients with AD, with no significant differences in CLA− T-cell numbers. The CLA+ TH 1/TH 2 and TC 1/TC 2 ratio was highly imbalanced in patients with AD (10 vs 3 [ P  = .005] and 19 vs 7 [ P  < .001], respectively). Positive correlations were found between frequencies of IL-13– and IL-22–producing CD4+ and CD8+ T cells ( r  = 0.5 and 0.8, respectively; P  < .0001), and frequencies of IL-13–producing CLA+ cells were also correlated with IgE levels and SCORAD scores. Patients with AD with skin infections had higher CD4+ IL-22+ and IL-17+ cell frequencies, which were highly significant among CLA− cells (IL-22: 3.7 vs 1.7 [ P  < .001] and IL-17: 1.7 vs 0.6 [ P  < .001]), with less significant effects among CLA+ T cells (IL-22: 11 vs 7.5, P  = .04). Conclusions Severe AD is accompanied by expansion of skin-homing TH 2/TC 2 and TH 22/TC 22 subsets with lower TH 1/TC 1 frequencies. These data create a critical basis for studying alterations in immune activation in adults and pediatric patients with AD.
ISSN:0091-6749
1097-6825
DOI:10.1016/j.jaci.2015.01.020