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

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Presentation on theme: "Severe atopic dermatitis is characterized by selective expansion of circulating TH2/TC2 and TH22/TC22, but not TH17/TC17, cells within the skin-homing."— Presentation transcript:

1 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  Tali Czarnowicki, MD, Juana Gonzalez, PhD, Avner Shemer, MD, Dana Malajian, BA, Hui Xu, MSc, Xiuzhong Zheng, MSc, Saakshi Khattri, MD, Patricia Gilleaudeau, NP, Mary Sullivan-Whalen, NP, Mayte Suárez-Fariñas, PhD, James G. Krueger, MD, PhD, Emma Guttman-Yassky, MD, PhD  Journal of Allergy and Clinical Immunology  Volume 136, Issue 1, Pages e7 (July 2015) DOI: /j.jaci Copyright © 2015 American Academy of Allergy, Asthma & Immunology Terms and Conditions

2 Fig 1 Gating strategy and frequency of IL-13 and IL-22 versus CLA positivity in CD4+ and CD8+ T cells in a healthy control subject and a representative patient with AD. A, Gating strategy. FSC, Forward scatter; SSC, side scatter. B, Representative plots of IL-13, IL-22, and CLA expression, showing higher IL-22+ and IL-13+ percentages in the patient with AD compared with the control subject, regardless of CLA positivity. Journal of Allergy and Clinical Immunology  , e7DOI: ( /j.jaci ) Copyright © 2015 American Academy of Allergy, Asthma & Immunology Terms and Conditions

3 Fig 2 TH2/TC2 skewing among CLA+ T cells. A and B, Higher IL-13+CLA+ T-cell frequencies in patients with severe AD (Fig 2, A) and patients with extrinsic AD (Fig 2, B). C, Higher IFN-γ+ to IL-13+ ratios in CLA+ CD4/CD8 T cells in control subjects. D, IL-13+CLA+ MFI levels are also higher in patients with severe and extrinsic AD. *P < .1, **P < .05, and ***P < .01. ns, Not significant. Journal of Allergy and Clinical Immunology  , e7DOI: ( /j.jaci ) Copyright © 2015 American Academy of Allergy, Asthma & Immunology Terms and Conditions

4 Fig 3 TH22/TC22 frequency in CLA+ and CLA− T cells. A, Significantly increased frequencies only in IL-22+CLA+ CD4/CD8 T cells in patients with AD. B, IL-22+CLA+ cell frequencies were significantly increased in patients with extrinsic AD. C, As opposed to equivalent values in control subjects, patients with AD had significantly higher IL-22 MFIs in CLA+ than CLA− T cells. D, Higher IL-22+IL-13+ double positive subset frequency in AD, correlates positively with SCORAD scores (E) and IgE levels (F). **P < .05 and ***P < .01. ns, Not significant. Journal of Allergy and Clinical Immunology  , e7DOI: ( /j.jaci ) Copyright © 2015 American Academy of Allergy, Asthma & Immunology Terms and Conditions

5 Fig 4 Skin-homing cytokine expression correlated with disease severity, IgE levels, and other T-cell subsets. A-D, Significant positive correlations between IL-13 expression and SCORAD scores or IgE levels (Fig 4, A and B) and between frequencies of IL-22 and IL-13 in CD4+ and even more in CD8+ CLA+ T cells (Fig 4, C and D) are shown. E-K, Significant negative correlations are shown between IFN-γ+ cell frequencies and disease severity (Fig 4, E and F), IgE levels (Fig 4, G and H), and IL-13 and IL-22 expression in CLA+ T cells (Fig 4, I-K). Journal of Allergy and Clinical Immunology  , e7DOI: ( /j.jaci ) Copyright © 2015 American Academy of Allergy, Asthma & Immunology Terms and Conditions

6 Fig 5 AD complicated by skin infection is characterized by increased IL-22 and IL-17 expression. A, Significantly increased frequencies of IL-22+ cells among both CLA+ and CLA− CD4 T cells in infected patients with AD. B and C, Trend toward decreased IFN-γ frequency in infected patients with AD in CD4+ and CD8+ T cells. D-G, Patients with infected AD have lower IFN-γ/IL-22 ratios among CLA−CD4+ T cells (Fig 5, D), higher IFN-γ+ and IL-22+ μ scores (with IFN-γ as a negative factor and IL-22 as a positive factor) in both CLA+ and CLA− T cells (Fig 5, E), higher IL-17 expression (Fig 5, F), and higher IFN-γ+ and IL-17+ μ scores (with IFN-γ as a negative factor and IL-17 as a positive factor; Fig 5, G) in CLA− T cells *P < .1, **P < .05, and ***P < .01. ns, Not significant. Journal of Allergy and Clinical Immunology  , e7DOI: ( /j.jaci ) Copyright © 2015 American Academy of Allergy, Asthma & Immunology Terms and Conditions

7 Fig E1 Frequency of IFN-γ+ in CLA+ and CLA− CD4+ and CD8+ T cells in patients with AD and control subjects. A and B, AD stratified by severity (dot size; Fig E1, A) or IgE levels showing decreased IFN-γ frequency (Fig E1, B) in patients with severe and extrinsic disease. C, Representative MFI plots of control subjects (blue) and patients with AD (red) showing an additional high-intensity peak in the control subject. D, IFN-γ+ ΔMFI. Patients with AD exhibit higher IFN-γ discrepancy between CLA− and CLA+ T cells that is significantly higher than that seen in control subjects. *P < .1, **P < .05, and ***P < .01. ns, Not significant. Journal of Allergy and Clinical Immunology  , e7DOI: ( /j.jaci ) Copyright © 2015 American Academy of Allergy, Asthma & Immunology Terms and Conditions

8 Fig E2 Cytokine positivity in absolute numbers (K/μL) in CD4+ and CD8+ CLA+ T cells. A and B, As opposed to patients with AD, control subjects had higher IFN-γ+CLA+ compared with IL-13+CLA+ cell frequencies among both CD4+ (Fig E2, A) and CD8+ (Fig E2, B) T cells. C and D, Patients with AD had higher IL-22+CLA+ cell frequencies among CD4+ (Fig E2, C) and CD8+ (Fig E2, D) T cells. **P < .05 and ***P < .01. ns, Not significant. Journal of Allergy and Clinical Immunology  , e7DOI: ( /j.jaci ) Copyright © 2015 American Academy of Allergy, Asthma & Immunology Terms and Conditions

9 Fig E3 Pearson correlation plot demonstrating correlations between all study T-cell subsets, IgE status, and disease severity. The colored gradient (−1 to +1) marks correlation strength; the red spectrum marks positive correlations, with deep red having the highest correlation coefficient. The blue color gradient marks negative correlations, with dark blue carrying the highest correlation coefficient. *P < .1, **P < .05, ***P < .01, and ****P < .001. Journal of Allergy and Clinical Immunology  , e7DOI: ( /j.jaci ) Copyright © 2015 American Academy of Allergy, Asthma & Immunology Terms and Conditions

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