Severe atopic dermatitis is characterized by selective expansion of circulating TH2/TC2 and TH22/TC22, but not TH17/TC17, cells within the skin-homing T-cell population

• Published in: Journal of allergy and clinical immunology Vol. 136; no. 1; pp. 104 - 115.e7
• Main Authors: Czarnowicki, Tali, Gonzalez, Juana, Shemer, Avner, Malajian, Dana, Xu, Hui, Zheng, Xiuzhong, Khattri, Saakshi, Gilleaudeau, Patricia, Sullivan-Whalen, Mary, Suárez-Fariñas, Mayte, Krueger, James G., Guttman-Yassky, Emma
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.07.2015; Elsevier Limited
• Subjects: Adolescent; Adult; Age; Aged; Alzheimer's disease; Antigens, Differentiation, T-Lymphocyte - metabolism; Atopic dermatitis; CD8-Positive T-Lymphocytes - immunology; Cell Movement; Cells, Cultured; cutaneous lymphocyte antigen; Cytokines; Dementia; Dermatitis, Atopic - immunology; Disease Progression; Expansion; Female; Humans; IFN-γ; IL-13; IL-22; Immunophenotyping; Interleukin-17 - metabolism; Interleukin-22; Interleukins - metabolism; Lymphocytes; Male; Membrane Glycoproteins - metabolism; Middle Aged; Population; Skin - immunology; skin infections; Staphylococcus infections; Studies; T cell; T-Lymphocyte Subsets - immunology; Th17 Cells - immunology; Th2 Cells - immunology; Young Adult; MFI; IFN-γ; AD; Atopic dermatitis; cutaneous lymphocyte antigen; PMA; T cell; skin infections; ICS; CLA; IL-13; IL-22
• ISSN: 0091-6749; 1097-6825; 1097-6825
• DOI: 10.1016/j.jaci.2015.01.020

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 TH9, TH17, and TH22 T-cell populations in human subjects. We sought to quantify TH1, TH2, TH9, TH17, and TH22 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. 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. We measured increased TH2/TC2/IL-13+ and TH22/TC22/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+ TH1/TH2 and TC1/TC2 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). Severe AD is accompanied by expansion of skin-homing TH2/TC2 and TH22/TC22 subsets with lower TH1/TC1 frequencies. These data create a critical basis for studying alterations in immune activation in adults and pediatric patients with AD.