TY - JOUR
T1 - 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
AU - Czarnowicki, Tali
AU - Gonzalez, Juana
AU - Shemer, Avner
AU - Malajian, Dana
AU - Xu, Hui
AU - Zheng, Xiuzhong
AU - Khattri, Saakshi
AU - Gilleaudeau, Patricia
AU - Sullivan-Whalen, Mary
AU - Suárez-Fariñas, Mayte
AU - Krueger, James G.
AU - Guttman-Yassky, Emma
N1 - Publisher Copyright:
© 2015 American Academy of Allergy, Asthma & Immunology.
PY - 2015
Y1 - 2015
N2 - 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 TH9, TH17, and TH22 T-cell populations in human subjects. Objective 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. 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 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). Conclusions 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.
AB - 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 TH9, TH17, and TH22 T-cell populations in human subjects. Objective 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. 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 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). Conclusions 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.
KW - Atopic dermatitis
KW - IFN-γ
KW - IL-13
KW - IL-22
KW - T cell
KW - cutaneous lymphocyte antigen
KW - skin infections
UR - http://www.scopus.com/inward/record.url?scp=84937022624&partnerID=8YFLogxK
U2 - 10.1016/j.jaci.2015.01.020
DO - 10.1016/j.jaci.2015.01.020
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C2 - 25748064
AN - SCOPUS:84937022624
SN - 0091-6749
VL - 136
SP - 104-115.e7
JO - Journal of Allergy and Clinical Immunology
JF - Journal of Allergy and Clinical Immunology
IS - 1
ER -