TY - JOUR
T1 - Early pediatric atopic dermatitis shows only a cutaneous lymphocyte antigen (CLA)+ TH2/TH1 cell imbalance, whereas adults acquire CLA+ TH22/TC22 cell subsets
AU - Czarnowicki, Tali
AU - Esaki, Hitokazu
AU - Gonzalez, Juana
AU - Malajian, Dana
AU - Shemer, Avner
AU - Noda, Shinji
AU - Talasila, Sreya
AU - Berry, Adam
AU - Gray, Jayla
AU - Becker, Lauren
AU - Estrada, Yeriel
AU - Xu, Hui
AU - Zheng, Xiuzhong
AU - Suárez-Fariñas, Mayte
AU - Krueger, James G.
AU - Paller, Amy S.
AU - Guttman-Yassky, Emma
N1 - Publisher Copyright:
© 2015 American Academy of Allergy, Asthma & Immunology.
PY - 2015/10
Y1 - 2015/10
N2 - 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-γ, IL-13, IL-9, IL-17, and IL-22 cytokines, defining TH1/cytotoxic T (TC) 1, TH2/TC2, TH9/TC9, TH17/TC17, and TH22/TC22 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+ TH2 T cells were markedly expanded in both children and adults with AD compared with those in control subjects, but decreases in CLA+ TH1 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 TH22 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 TH2 activation within skin-homing T cells might drive AD in children and that reduced counterregulation by TH1 T cells might contribute to excess TH2 activation. TH22 "spreading" of AD is not seen in young children and might be influenced by immune development, disease chronicity, or recurrent skin infections.
AB - 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-γ, IL-13, IL-9, IL-17, and IL-22 cytokines, defining TH1/cytotoxic T (TC) 1, TH2/TC2, TH9/TC9, TH17/TC17, and TH22/TC22 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+ TH2 T cells were markedly expanded in both children and adults with AD compared with those in control subjects, but decreases in CLA+ TH1 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 TH22 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 TH2 activation within skin-homing T cells might drive AD in children and that reduced counterregulation by TH1 T cells might contribute to excess TH2 activation. TH22 "spreading" of AD is not seen in young children and might be influenced by immune development, disease chronicity, or recurrent skin infections.
KW - Atopic dermatitis
KW - CD69
KW - HLA-DR
KW - IFN-γ
KW - IL-13
KW - IL-22
KW - T cell
KW - cutaneous lymphocyte antigen
KW - inducible costimulator
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U2 - 10.1016/j.jaci.2015.05.049
DO - 10.1016/j.jaci.2015.05.049
M3 - Article
C2 - 26242300
AN - SCOPUS:84943457665
SN - 0091-6749
VL - 136
SP - 941-951.e3
JO - Journal of Allergy and Clinical Immunology
JF - Journal of Allergy and Clinical Immunology
IS - 4
ER -