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

Tali Czarnowicki, Hitokazu Esaki, Juana Gonzalez, Dana Malajian, Avner Shemer, Shinji Noda, Sreya Talasila, Adam Berry, Jayla Gray, Lauren Becker, Yeriel Estrada, Hui Xu, Xiuzhong Zheng, Mayte Suárez-Fariñas, James G. Krueger, Amy S. Paller, Emma Guttman-Yassky

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish
Pages (from-to)941-951.e3
JournalJournal of Allergy and Clinical Immunology
Volume136
Issue number4
DOIs
Publication statusPublished - Oct 1 2015

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Atopic Dermatitis
Lymphocytes
Pediatrics
Antigens
Skin
T-Lymphocytes
Inducible T-Cell Co-Stimulator Protein
T-Lymphocyte Subsets
HLA-DR Antigens
Interleukin-9
CD8 Antigens
CD4 Antigens
Interleukin-13
Interleukin-17
Immune System Diseases
Population
Flow Cytometry
Cell Count
Cytokines

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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Early pediatric atopic dermatitis shows only a cutaneous lymphocyte antigen (CLA)+ TH2/TH1 cell imbalance, whereas adults acquire CLA+ TH22/TC22 cell subsets. / Czarnowicki, Tali; Esaki, Hitokazu; Gonzalez, Juana; Malajian, Dana; Shemer, Avner; Noda, Shinji; Talasila, Sreya; Berry, Adam; Gray, Jayla; Becker, Lauren; Estrada, Yeriel; Xu, Hui; Zheng, Xiuzhong; Suárez-Fariñas, Mayte; Krueger, James G.; Paller, Amy S.; Guttman-Yassky, Emma.

In: Journal of Allergy and Clinical Immunology, Vol. 136, No. 4, 01.10.2015, p. 941-951.e3.

Research output: Contribution to journalArticle

Czarnowicki, T, Esaki, H, Gonzalez, J, Malajian, D, Shemer, A, Noda, S, Talasila, S, Berry, A, Gray, J, Becker, L, Estrada, Y, Xu, H, Zheng, X, Suárez-Fariñas, M, Krueger, JG, Paller, AS & Guttman-Yassky, E 2015, 'Early pediatric atopic dermatitis shows only a cutaneous lymphocyte antigen (CLA)+ TH2/TH1 cell imbalance, whereas adults acquire CLA+ TH22/TC22 cell subsets', Journal of Allergy and Clinical Immunology, vol. 136, no. 4, pp. 941-951.e3. https://doi.org/10.1016/j.jaci.2015.05.049
Czarnowicki, Tali ; Esaki, Hitokazu ; Gonzalez, Juana ; Malajian, Dana ; Shemer, Avner ; Noda, Shinji ; Talasila, Sreya ; Berry, Adam ; Gray, Jayla ; Becker, Lauren ; Estrada, Yeriel ; Xu, Hui ; Zheng, Xiuzhong ; Suárez-Fariñas, Mayte ; Krueger, James G. ; Paller, Amy S. ; Guttman-Yassky, Emma. / Early pediatric atopic dermatitis shows only a cutaneous lymphocyte antigen (CLA)+ TH2/TH1 cell imbalance, whereas adults acquire CLA+ TH22/TC22 cell subsets. In: Journal of Allergy and Clinical Immunology. 2015 ; Vol. 136, No. 4. pp. 941-951.e3.
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title = "Early pediatric atopic dermatitis shows only a cutaneous lymphocyte antigen (CLA)+ TH2/TH1 cell imbalance, whereas adults acquire CLA+ TH22/TC22 cell subsets",
abstract = "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.",
author = "Tali Czarnowicki and Hitokazu Esaki and Juana Gonzalez and Dana Malajian and Avner Shemer and Shinji Noda and Sreya Talasila and Adam Berry and Jayla Gray and Lauren Becker and Yeriel Estrada and Hui Xu and Xiuzhong Zheng and Mayte Su{\'a}rez-Fari{\~n}as and Krueger, {James G.} and Paller, {Amy S.} and Emma Guttman-Yassky",
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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

PY - 2015/10/1

Y1 - 2015/10/1

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.

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