Background/Purpose: 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 resident IL-23⁺ 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 IL-23R⁺ CD8⁺ T cells and measurements of disease activity, as well as between IL-17⁺ or IL-22⁺ MAIT cells and disease activity.

Conclusion:  These preliminary results suggest that the peripheral blood of patients with AS is enriched in IL-23R⁺ CD8⁺ 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 IL-22 production. This remains to be clarified by future and complementary studies.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/increased-frequencies-of-il-23r-positive-t-cells-and-il-22-and-il-17-producing-mait-cells-in-the-peripheral-blood-of-patients-with-ankylosing-spondylitis-preliminary-results/