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bioRxiv · 10.1101/2022.01.17.475829

Polyfunctional IL-17A+ MAIT cells are expanded in the peripheral blood of patients with HLA-B27+ axial spondyloarthritis

Lefton, M.·Sharma, N.·Patel, A. R.·Sparks, J. A.·Ermann, J.
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Abstract

ObjectivesStudies in axial spondyloarthritis (axSpA) have yielded conflicting results regarding the identity of the major IL-17A-producing lymphocyte populations. The goal of this study was to comprehensively assess the production of IL-17A and related cytokines by peripheral blood lymphocytes in axSpA. MethodsPeripheral blood mononuclear cells were isolated from patients with axSpA and healthy controls matched for age, sex and HLA-B27 status. Unstimulated cells and cells activated with PMA/Ionomycin were analyzed by 25-parameter fluorescent flow cytometry. Data were analyzed by hierarchical gating, UMAP and SPICE. ResultsExcept for a reduced frequency of mucosal-associated invariant T (MAIT) cells and natural killer (NK) cells, there were no other significant differences in abundance of major lymphocyte populations in axSpA patients compared with controls. Increased IL-17A production in axSpA was observed in total non-B lymphocytes and in MAIT cells. The fraction of MAIT cells expressing the tissue residency markers CD69 and CD103 was increased in axSpA. CD103 positive MAIT cells were enriched for IL-17A producers. axSpA patients demonstrated an expansion of MAIT cell subsets producing IL-17A, IL-17F, GM-CSF and TNF. This expansion was only observed in HLA-B27+ patients. ConclusionsWe document an expansion of polyfunctional IL-17A+ MAIT cells in the peripheral blood of HLA-B27+ patients with axSpA. These results are consistent with the implied role of intestinal dysbiosis or inflammation in axSpA pathogenesis. Key messagesWhat is already known about this subject? O_LIVarious IL-17A-producing lymphocyte populations have been implicated in the pathogenesis of axSpA. C_LI What does this study add? O_LIPolyfunctional MAIT cells capable of producing IL-17A, IL-17F, GM-CSF and TNF are expanded in the peripheral blood of HLA-B27+ patients with axSpA. C_LI How might this impact on clinical practice or future developments? O_LIOverproduction of IL-17A by MAIT cells is the most consistent finding of peripheral blood lymphocyte studies in axSpA. C_LIO_LIOur data support the pathogenetic link between intestinal and axial inflammation in axSpA. C_LI

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Lefton, M., Sharma, N., Patel, A. R., Sparks, J. A., Ermann, J.. 2022-01-18. Polyfunctional IL-17A+ MAIT cells are expanded in the peripheral blood of patients with HLA-B27+ axial spondyloarthritis. https://doi.org/10.1101/2022.01.17.475829

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