Increased IL-22- and IL-17A-Producing Mucosal-Associated Invariant T Cells in the Peripheral Blood of Patients With Ankylosing Spondylitis.

Éric Toussirot,Damien Gabriel,Caroline Laheurte,Béatrice Gaugler,Philippe Saas

doi:10.3389/fimmu.2018.01610

Abstract

The IL-23/T helper 17 (Th17) axis plays an important role in joint inflammation in ankylosing spondylitis (AS). Conventional CD4+ Th17 cells are a major source of IL-17A. IL-22 is another cytokine implicated in AS pathophysiology and is produced by Th17 and Th22 cells. In this study, we aimed to analyze conventional and non-conventional T cell subsets producing IL-17A and IL-22 in patients with AS. We thus evaluated the intracellular staining for IL-17A, IL-22, and IFN-γ in peripheral blood mononuclear cells of 36 patients with AS and 55 age- and sex-matched healthy controls (HC). Conventional CD4+ and CD8+ T cells, γδ T cells, and mucosal-associated invariant T (MAIT) cells were evaluated. In patients with AS, we found a decreased frequency and number of γδ T cells, of MAIT cells and of IFN-γ+ CD4+ and CD8+ T cells. Th17-related IL-17A+/IFN-γ− CD4+ T cells were decreased in AS. The number of IL-22+ MAIT cells was higher in AS compared with HC, as well as the number of IFN-γ+/IL-17A+ MAIT cells. The number of IFN-γ−/IL-17A+ MAIT cells was higher only in female patients with AS compared with female HC. The cellular source of IL-17A was thus not restricted to conventional Th17 CD4+ T cells and might involve innate-like T cells, such as MAIT cells. Circulating MAIT cells producing IL-22 were increased in AS. These results strengthen the importance of innate and innate-like sources of IL-17A and/or IL-22.

Highlights

Ankylosing spondylitis (AS) is the prototypical and most common form of spondyloarthritis (SpA)
Patients had active disease according to Bath ankylosing spondylitis disease activity index (BASDAI) and ankylosing spondylitis disease activity score (ASDAS) and had higher C-reactive protein (CRP) levels compared with healthy controls (HC) (p = 0.008)
Only few studies have characterized the cells that are responsive to IL-23 and/or produce IL-17A and IL-22 in the peripheral blood of patients with AS, and at sites of disease inflammation

Summary

Introduction

Ankylosing spondylitis (AS) is the prototypical and most common form of spondyloarthritis (SpA). AS has been found to be associated with a genetic polymorphism of the IL-23 receptor (IL-23R) gene [3], and IL-23 is a maturation and growth factor for IL-17A-secreting cells. HLA-B27, a major genetic predisposing factor for AS, has the property to be misfolded during the Cytokine-Producing MAIT in AS assembly of its heavy chain in the endoplasmic reticulum, and this phenomenon generates IL-23 production [4]. Circulating IL-17A+ CD4+ T cells and IL-17A-producing γδ T cells are expanded in AS, together with increased serum concentrations of IL-23 and IL-17A [5]. IL-23 overexpression in a mouse model of arthritis induces a SpA-like disease characterized by enthesitis with an inflammatory infiltrate containing IL-23R+ resident T cells expressing retinoid acid receptor-related orphan receptor γt, and these cells produce IL-17A and IL-22 [6]. Therapeutic trials targeting IL-17A have been proven to be effective in patients with AS [7]

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