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IL-22–producing “T22” T cells account for upregulated IL-22 in atopic dermatitis despite reduced IL-17–producing TH17 T cells  Kristine E. Nograles, MD,

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Presentation on theme: "IL-22–producing “T22” T cells account for upregulated IL-22 in atopic dermatitis despite reduced IL-17–producing TH17 T cells  Kristine E. Nograles, MD,"— Presentation transcript:

1 IL-22–producing “T22” T cells account for upregulated IL-22 in atopic dermatitis despite reduced IL-17–producing TH17 T cells  Kristine E. Nograles, MD, Lisa C. Zaba, PhD, Avner Shemer, MD, Judilyn Fuentes-Duculan, MD, Irma Cardinale, MSc, Toyoko Kikuchi, MSc, Michal Ramon, MD, Reuven Bergman, MD, James G. Krueger, MD, PhD, Emma Guttman-Yassky, MD, MSc  Journal of Allergy and Clinical Immunology  Volume 123, Issue 6, Pages e2 (June 2009) DOI: /j.jaci Copyright © 2009 American Academy of Allergy, Asthma & Immunology Terms and Conditions

2 Fig 1 The cytokine microenvironment in AD and psoriasis skin lesions. Quantitative RT-PCR analysis of cytokine mRNA expression normalized to hARP in skin biopsies of lesional AD, psoriasis, and normal skin. TH1/TH17 (IFN-γ/IL-17) polarization was observed in psoriasis, TH2 (IL-13) polarization in AD, with upregulation of IL-22 expression in both diseases. ∗P < .05; ∗∗P < .01; ∗∗∗P < .005. Journal of Allergy and Clinical Immunology  , e2DOI: ( /j.jaci ) Copyright © 2009 American Academy of Allergy, Asthma & Immunology Terms and Conditions

3 Fig 2 Circulating CD3+ T-cell profiles are similar in AD and psoriasis. A, FACS gating used in the analysis of peripheral blood. B, Frequencies of circulating cytokine-producing CD4+ and CD8+ T cells did not differ between AD and psoriasis. Graphs summarize cytokine-producing CD4+ and CD8+ T-cell subsets in AD and psoriasis blood. Representative FACS plots are shown. SSC-A, side scatter; FSC-A, forward scatter. Journal of Allergy and Clinical Immunology  , e2DOI: ( /j.jaci ) Copyright © 2009 American Academy of Allergy, Asthma & Immunology Terms and Conditions

4 Fig 3 AD and psoriasis lesions have distinct T-cell profiles. A, Graph of CD4+ T-cell subsets in AD and psoriasis lesions showing TH1/TH17 (IFN-γ/IL-17) polarization in psoriasis, TH2 (IL-4) in AD, and similar IL-22+CD4+ frequencies in both. Representative FACS plots follow. B, Graph of skin CD8+ T-cell subsets showing Tc1 (IFN-γ) polarity in psoriasis and IL-22+CD8+ polarity in AD. Representative FACS plots follow. ∗P < .05; ∗∗P < .01; ∗∗∗P < .005. Journal of Allergy and Clinical Immunology  , e2DOI: ( /j.jaci ) Copyright © 2009 American Academy of Allergy, Asthma & Immunology Terms and Conditions

5 Fig 4 Unique IL-22–producing CD4+ and CD8+ subsets are abundant in AD lesions. A, FACS gating used in the analysis of IL-22–producing T cells. B, Majority of IL-22+CD4+ T cells in AD are not TH1, TH2, or TH17 cells. Psoriasis IL-22 is produced by TH1, TH17, and “TH22” cells. Representative FACS plots shown. C, Majority of IL-22–producing CD8+ T cells in AD are “Tc22” cells. Journal of Allergy and Clinical Immunology  , e2DOI: ( /j.jaci ) Copyright © 2009 American Academy of Allergy, Asthma & Immunology Terms and Conditions

6 Fig 5 IL-22+CD8+ T-cell frequency correlates with disease severity. A, Immunofluorescence showing abundant CD8+ T cells in AD dermis. Bar, 100 μm. B, Linear regression showing positive correlation between IL-22–producing CD8+ T cells (“Tc22”) and AD clinical severity (SCORAD; r = 0.78; P < .05). C, Linear regression of IL-22–producing CD4+ T cells (“TH22”) showing positive trend with disease severity but not statistically significant. Journal of Allergy and Clinical Immunology  , e2DOI: ( /j.jaci ) Copyright © 2009 American Academy of Allergy, Asthma & Immunology Terms and Conditions

7 Fig 6 Model of major T cells and their cytokines in chronic skin lesions of psoriasis vs AD. In psoriasis, TH1 cells produce IFN-γ, TH17 cells produce both IL-17 and IL-22 cytokines, and “TH22” cells produce IL-22 but not IL-17. Upregulated IL-17 axis in psoriasis results in increased production of antimicrobial proteins, neutrophil chemoattractants, and CCL20 chemokine, whereas upregulated IL-22 causes epidermal acanthosis. In AD, the TH2 cytokines IL-4 and IL-13 potentially inhibit TH17 T-cell activity, resulting in reduced IL-17 effects. Both “TH22” and “Tc22” T cells in AD are responsible for significantly increased IL-22 levels. The upregulated IL-22 in chronic AD skin may explain the marked acanthosis that is histologically similar to psoriasis, and the defective terminal differentiation seen in this disease. STAT, Signal transducer and activator of transcription; hBD-2, human B-defensin 2; LL-37, cathelicidin; IL-17R, interleukin 17 receptor; IL-22R, interleukin 22 receptor. Journal of Allergy and Clinical Immunology  , e2DOI: ( /j.jaci ) Copyright © 2009 American Academy of Allergy, Asthma & Immunology Terms and Conditions

8 Fig E1 Similar composition of cells isolated from AD and psoriasis lesions. Percentages of isolated T cells, CD4+ TH cells, and CD8+ T-cytotoxic cells are statistically similar between AD and psoriasis skin lesions. Journal of Allergy and Clinical Immunology  , e2DOI: ( /j.jaci ) Copyright © 2009 American Academy of Allergy, Asthma & Immunology Terms and Conditions

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