Background Ankylosing spondylitis (AS) is the prototypic and most common form of spondyloarthritis (SpA). It was recently suggested that IL-23 could play a pivotal role in the pathophysiology of SpA. Indeed, there is a strong genetic association of SpA with polymorphisms of the IL-23 receptor (IL-23R) gene. In experimental models, IL-23 is produced during the misfolding phenomenon of HLA-B27 heavy chain in the endoplasmic reticulum. Furthermore, in animal models, IL-23 overexpression induced a SpA-like disease via IL-23+ resident T cells infiltrating entheseal structures and producing IL-17 and IL-22. In addition, there is an increased number of circulating cells producing IL-17 in patients with AS. Recent data also suggested that IL-17A is a potential target in the treatment of patients with AS.
Objectives Cells that expressed IL-23R as well as those producing IL-17 and/or IL-22 have been poorly characterized in AS and/or SpA. Thus, we aimed to better delineate the peripheral blood T cells that expressed IL-23R and the IL-17 and IL-22 producing cell subsets, notably conventional T cells as well as mucosal associated invariant T cells (MAIT) in patients with AS.
Methods 36 patients with AS (modified NY criteria; 27 M; age: 44.7 ± 2.6, disease duration: 12.7 ± 1.6; all under NSAIDs or traditional DMARDs) and 31 healthy controls (HC) (8 M; age: 46 ± 2.3) were evaluated. For each subject, peripheral blood T cell subsets were assessed using multi-color flow cytometry. Intracellular cytokine IL-17A, IL-22 and IFN-γ were evaluated after phorbol myristate acetate and ionomycine activation and permeabilization and analysed by flow cytometry. MAIT cells were identified by using TCRVα7.2 specific monoclonal antibodies. IL-22 serum levels were determined by ELISA using commercially available kit.
Results the number and percentage of CD3+ T cells, CD3+CD4+ and CD3+CD8+ T cells were comparable between patients and HC. Circulating IL-22 levels did not differ between patients and HC (22.6 ± 8.4 vs 15.1 ± 4.4 pg/ml, p=0.7). IFN-γ producing CD4+ and CD8+ T cells were decreased in AS compared to HC (4.6 ± 1.7 vs 11.4 ± 2.5% and 23.3 ± 1.9 vs 34.3 ± 2.3%, respectively, p=0.005 and p=0.002). CD8+ T cells expressing IL-23R were significantly increased in AS: 72.8 ± 1.5 vs 65.2 ± 2% (p=0.009). The percentage of MAIT T cells did not differ between patients and HC but we found an increased percentage of MAIT cells that produced IL-17 and IL-22: MAIT IFN-γ– IL-17+: 0.43 ± 0.1 vs 0.12 ± 0.008%, p=0.006; MAIT IFN-γ– IL-22+: 0.83 ± 0.1 vs 0.3 ± 0.1%, p=0.004. No correlation was found between the percentage of CD8+ IL-23R+ T cells and measurements of disease activity as well as between IL-17+ or IL-22+ MAIT cells and disease activity.
Conclusions These preliminary results suggest that the peripheral blood of patients with AS is enriched in CD8+ IL-23R+ T cells as well as IL-17 and IL-22 producing MAIT cells. Since MAIT cells are involved in antibacterial immunity and bacterial agents are potentially involved in SpA, our preliminary data suggest that this T cell subset could potentially play a role in AS via IL-17 and IL22 production. This remains to be clarified by future and complementary studies.
Disclosure of Interest None declared