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Streptococcus pyogenes–induced cutaneous lymphocyte antigen–positive T cell– dependent epidermal cell activation triggers TH17 responses in patients with.

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Presentation on theme: "Streptococcus pyogenes–induced cutaneous lymphocyte antigen–positive T cell– dependent epidermal cell activation triggers TH17 responses in patients with."— Presentation transcript:

1 Streptococcus pyogenes–induced cutaneous lymphocyte antigen–positive T cell– dependent epidermal cell activation triggers TH17 responses in patients with guttate psoriasis  Ester Ruiz-Romeu, BSc, Marta Ferran, MD, Marc Sagristà, MD, Julià Gómez, PhD, Ana Giménez-Arnau, MD, PhD, Krisztina Herszenyi, MD, Péter Hóllo, MD, PhD, Antonio Celada, MD, PhD, Ramon Pujol, MD, PhD, Luis F. Santamaria-Babí, PhD  Journal of Allergy and Clinical Immunology  Volume 138, Issue 2, Pages e6 (August 2016) DOI: /j.jaci Copyright © 2016 American Academy of Allergy, Asthma & Immunology Terms and Conditions

2 Fig 1 SE-activated cocultures of CLA+ T cells and epidermal cells from patients with GP produce high levels of psoriasis-associated cytokines. Cocultures of supernatants from 14 patients with GP and 6 healthy control (CTRL) samples were collected at day 5, and IL-17A (A), IL-17F (B), IFN-γ (C), IL- 6 (D), TNF-α (E), and IL-8 (F) concentrations were measured. Data are represented by box plots (minimum to maximum and median ± interquartile range). Cytokine production by cocultures stimulated with SE were compared with basal cytokine values by using the Mann-Whitney U test: #P < .05 and ##P < .01. SE-stimulated conditions were compared by using the Kruskal-Wallis ANOVA test, followed by Dunn multiple comparison: *P < .05, **P < .01, and ***P < .001. Cell types and SE presence (+) for each coculture condition are defined below the x-axis. Journal of Allergy and Clinical Immunology  , e6DOI: ( /j.jaci ) Copyright © 2016 American Academy of Allergy, Asthma & Immunology Terms and Conditions

3 Fig 2 TH17 response is increased in HLA-Cw6+ patients with GP with previous pharyngitis. A-F, Cytokine production by cohort 1 (C-1, n = 6; except for IL-8 CLA−/Epi/SE, n = 3) and cohort 2 (C-2, n = 5). Data are expressed as box plots (minimum to maximum and median ± interquartile range). The Mann-Whitney U test was used to compare cytokine production: *P < .05 and **P < .01. NS, Not significant. Cell types and SE presence (+) for each coculture condition are defined below the x-axis. Linear correlation between cohort 1 SE-activated CLA+/Epi production of IL-17A (G) or IFN-γ (H) with time elapsed since disease onset. Journal of Allergy and Clinical Immunology  , e6DOI: ( /j.jaci ) Copyright © 2016 American Academy of Allergy, Asthma & Immunology Terms and Conditions

4 Fig 3 Supernatants from psoriatic cohort 1–derived CLA+/Epi cocultures trigger a higher expression of psoriasis-associated transcripts in keratinocytes. A, Gene induction capacity of SE-activated CLA+/CLA− coculture supernatants from cohort 1 (GP C-1; n = 6) is compared with that of cohort 2 (GP C-2; n = 5) and control subjects (CTRL; n = 5). The Mann-Whitney U test was used for median comparisons: *P < .05 and **P < .01. B, Correlation between IL-17A concentrations of 5-day supernatants from SE-activated CLA+/Epi cocultures and the mRNA levels induced in keratinocytes. FI, Fold increase. Journal of Allergy and Clinical Immunology  , e6DOI: ( /j.jaci ) Copyright © 2016 American Academy of Allergy, Asthma & Immunology Terms and Conditions

5 Fig 4 Expression of the skin barrier–associated genes FLG and LOR is downregulated by SE-activated CLA+/Epi coculture supernatants from GP cohort 1 samples. A, mRNA fold increase (FI) expression levels in keratinocytes treated with SE-activated CLA+/CLA− coculture supernatants from GP cohort 1 (GP C-1; n = 6), GP cohort 2 (GP C-2; n = 4), or healthy control subjects (CTRL; n = 5) samples. The Mann-Whitney U test was used for median comparisons: *P < .05 and **P < .01. B, Linear correlation between IL-17A concentrations within SE-activated CLA+/Epi coculture supernatants and respective mRNA expression in keratinocytes. Journal of Allergy and Clinical Immunology  , e6DOI: ( /j.jaci ) Copyright © 2016 American Academy of Allergy, Asthma & Immunology Terms and Conditions

6 Fig E1 TH17-predominant response in CLA+ T cells from patients with GP cultured with autologous epidermal cells induced by SE. A and B, Wilcoxon paired test analysis (marked as arrows) comparing IL-17A, IL-17F, and IFN-γ production in culture supernatants. C, Detailed paired data of IL-17A and IFN-γ cytokine concentrations from SE-activated CLA−/Epi cocultures (n = 13) from GP samples expressed as dots for each subject. NS, Not significant. Journal of Allergy and Clinical Immunology  , e6DOI: ( /j.jaci ) Copyright © 2016 American Academy of Allergy, Asthma & Immunology Terms and Conditions

7 Fig E2 Pairwise comparison indicates higher production of IL-17A than IFN-γ in cohort 1 CLA+/Epi/SE cocultures. Wilcoxon paired test analysis (marked as arrows) compared IL-17A, IL-17F, and IFN-γ production in supernatants from CLA+/Epi/SE (A) and CLA−/Epi/SE (B) cocultures. NS, Not significant. Journal of Allergy and Clinical Immunology  , e6DOI: ( /j.jaci ) Copyright © 2016 American Academy of Allergy, Asthma & Immunology Terms and Conditions

8 Fig E3 IFN-γ from SE-activated CLA+/Epi cell cocultures does not present a significant correlation with upregulation of gene expression in keratinocytes. Correlation between the contents of IFN-γ in the GP-derived supernatants from CLA+/Epi cocultures (cohort 1, n = 6; cohort 2, n = 5) and their respective mRNA levels of induction/reduction in keratinocytes. Journal of Allergy and Clinical Immunology  , e6DOI: ( /j.jaci ) Copyright © 2016 American Academy of Allergy, Asthma & Immunology Terms and Conditions


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