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Streptococcus Induces Circulating CLA+ Memory T-Cell-Dependent Epidermal Cell Activation in Psoriasis  Marta Ferran, Ana B. Galván, Catalina Rincón, Ester.

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Presentation on theme: "Streptococcus Induces Circulating CLA+ Memory T-Cell-Dependent Epidermal Cell Activation in Psoriasis  Marta Ferran, Ana B. Galván, Catalina Rincón, Ester."— Presentation transcript:

1 Streptococcus Induces Circulating CLA+ Memory T-Cell-Dependent Epidermal Cell Activation in Psoriasis  Marta Ferran, Ana B. Galván, Catalina Rincón, Ester R. Romeu, Marc Sacrista, Erika Barboza, Ana Giménez-Arnau, Antonio Celada, Ramon M. Pujol, Luis F. Santamaria-Babí  Journal of Investigative Dermatology  Volume 133, Issue 4, Pages (April 2013) DOI: /jid Copyright © 2013 The Society for Investigative Dermatology, Inc Terms and Conditions

2 Figure 1 Streptococcal extract (SE) induces upregulation of mRNA for ifn-γ, il-17, il-22, and ip-10 in psoriatic cutaneous lymphocyte–associated antigen (CLA)+ T cells cultured with lesional autologous epidermal cells. Culture of freshly isolated circulating CLA+/CLA− CD45RO+CD3+ cells with autologous epidermal cells obtained from lesional psoriatic skin was incubated with or without SE. A time-course analysis of ifn-γ, il-17, il-22, and ip-10 mRNA expression was performed. RNA was taken at the indicated times after activation and determined by real-time PCR. (a) Data presented are from three psoriatic patients and (b) from three controls. Journal of Investigative Dermatology  , DOI: ( /jid ) Copyright © 2013 The Society for Investigative Dermatology, Inc Terms and Conditions

3 Figure 2 Streptococcal extract (SE) induces IFN-γ and IL-17 production in cutaneous lymphocyte–associated antigen (CLA)+ T cells cultured with autologous lesional epidermal psoriatic cells. Supernatants from cultured memory T cells (CLA+/CLA−) and autologous lesional epidermal psoriatic cells stimulated with SE or with Staphylococcus aureus enterotoxin B (SEB) for controls were analyzed for IFN-γ and IL-17 after 48hours of culture by ELISA. (a–d) Data are presented from five psoriatic patients (p) and three controls (c) as net cytokine production. Journal of Investigative Dermatology  , DOI: ( /jid ) Copyright © 2013 The Society for Investigative Dermatology, Inc Terms and Conditions

4 Figure 3 Supernatants of streptococcal extract (SE)–activated cutaneous lymphocyte–associated antigen (CLA)+ T cells and epidermal cells generate epidermal hyperplasia in vivo. Intradermal injection of supernatants from CLA+ T cells cultured with lesional epidermal cells activated with SE induces in vivo epidermal hyperplasia in Balb/c mice. Supernatant from day 6 of the culture was injected intradermally in Balb/c mice daily for 4 days, and epidermal hyperplasia was evaluated at day 4. (a–c) Results are shown with histological images of skin biopsies (hematoxylin and eosin) and a comparative graphic of epidermis thickness (in micrometers) after supernatant injections in four mice (P<0.001). Bar=50μm. Journal of Investigative Dermatology  , DOI: ( /jid ) Copyright © 2013 The Society for Investigative Dermatology, Inc Terms and Conditions

5 Figure 4 Streptococcal extract–induced upregulation of mRNA for ifn-γ, il-17, il-22, ip-10, tnf-α, and il-8 in cultures of cutaneous lymphocyte–associated antigen (CLA)+/CLA− T cells of nonlesional epidermal cells of psoriasis patients. Upregulated gene transcription in the culture 24hours after activation. Data are presented for two patients with nonlesional epidermal cells. Journal of Investigative Dermatology  , DOI: ( /jid ) Copyright © 2013 The Society for Investigative Dermatology, Inc Terms and Conditions

6 Figure 5 Streptococcal extract–induced upregulation in gene transcription for ifn-γ, il-17, il-22, and ip-10 after 24hours of activation of cutaneous lymphocyte–associated antigen (CLA)+ memory T cells and epidermal cells correlates with antistreptolysin O (ASO) serum levels in psoriatic patients. Patients are identified by number and psoriasis type (C, chronic; G, guttate). Journal of Investigative Dermatology  , DOI: ( /jid ) Copyright © 2013 The Society for Investigative Dermatology, Inc Terms and Conditions

7 Figure 6 Streptococcal extract (SE)–induced upregulation of IL-17A, IFN-γ, IL-6, and TNF-α in cultures of cutaneous lymphocyte–associated antigen (CLA)+ T cells and epidermal cells depends on HLA class I and HLA class II. Three experiments conducted with patients p18, p19, and p23 are presented. (a) Cytokines induced by SE on CLA+ memory T cells and epidermal cells are inhibited with anti-HLA class I and anti class II blocking antibodies; data are presented as net values. (b) The mean percentage inhibition respect isotype is significantly higher for anti-HLA class II than anti-HLA class I; IL-17A (P<0.0001), IFN-γ (P<0.03), and TNF-α (P<0.001). Journal of Investigative Dermatology  , DOI: ( /jid ) Copyright © 2013 The Society for Investigative Dermatology, Inc Terms and Conditions


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