CLA+ T Cell Response to Microbes in Psoriasis.

Carmen De Jesús-Gil,Ester Ruiz-Romeu,Gustavo Deza,Anca Chiriac,Péter Hóllo,Luis F Santamaria-Babí,Marta Ferran,Ramon M Pujol,Antonio Celada

doi:10.3389/fimmu.2018.01488

Abstract

Streptococcus pyogenes throat infection is a clinically relevant trigger of both guttate and chronic plaque psoriasis, and it provides an ideal context in which to study the pathogenesis of these diseases using an antigen-dependent approach. Circulating cutaneous lymphocyte-associated antigen (CLA) positive (+) memory T cells are a subset of peripheral lymphocytes whose phenotype and function are related to immunological mechanisms in the skin. These cells are considered peripheral biomarkers of T-cell-mediated skin diseases. The coculture of autologous epidermal cells with CLA+ T cells from psoriasis patients activated by S. pyogenes allows the reproduction of the ex vivo initial molecular events that occur during psoriatic lesion formation. With cooperation of autologous epidermal cells, S. pyogenes selectively activates CLA+ T cells both in guttate and plaque psoriasis, inducing key mediators, including an IL-17 response. Here, we explore potential new mechanisms of psoriasis development including the influence of HLA-Cw6 on S. pyogenes CLA+ T cell activation in guttate psoriasis, the relevance of IL-9 on microbe induced IL-17 response in guttate and plaque psoriasis, and novel effector functions of Candida albicans. This review will summarize recent knowledge of psoriatic mechanisms elicited by microbes that have been studied through an innovative translational perspective based on CLA+ T cell-mediated cutaneous immune response.

Highlights

Molecular studies of psoriasis lesions and patients have allowed translational research to generate potent and novel therapies [1]
Since S. pyogenes induces both IL-9 and IL-17A, we examined the interaction between these two cytokines in cutaneous lymphocyte-associated antigen (CLA)+ T cells
Our studies have shown that, in chronic plaque psoriasis (CPP) patients without clinical evidence of S. pyogenes infection, only CLA+ T cells respond to this microbe in comparison to healthy controls

Summary

INTRODUCTION

Molecular studies of psoriasis lesions and patients have allowed translational research to generate potent and novel therapies [1]. Our studies have shown that, in CPP patients without clinical evidence of S. pyogenes infection, only CLA+ T cells respond to this microbe in comparison to healthy controls This observation indicates that psoriasis patients present an adaptive immune response to S. pyogenes through IL-17A, IL-17F, IL-9, and IFN-γ production [20, 21, 24] and suggests that S. pyogenes modulates the response of the CLA+ T cells that maintain psoriatic lesions, i.e., pyogenes infection has been describe to participate in CPP infection, since higher levels of IgG against S. pyogenes proteins are detected in psoriasis patients in comparison to healthy controls [25]. Some studies have reported the presence of the genera Streptococcus in normal and psoriatic skin [26] and the isolation of S. pyogenes in the skin of GP patients [4], probably leading to cutaneous immunization and a CLA+ T cell-restricted response in psoriasis

IN PSORIASIS

RESPONSE IN PSORIASIS

Findings

AUTHOR CONTRIBUTIONS