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Objective  The importance of interleukin‐17A (IL‐17A) in the pathogenesis of axial spondyloarthritis (SpA) has been demonstrated by the success of IL‐17A blockade. However, the nature of the cell populations that produce this important proinflammatory cytokine remains poorly defined. We undertook this study to characterize the major IL‐17A–producing blood cell populations in the peripheral blood of patients with axial SpA, with a focus on mucosal‐associated invariant T (MAIT) cells, a population known to be capable of producing IL‐17.    Methods  We evaluated IL‐17A production from 5 sorted peripheral blood cell populations, namely, MAIT cells, γδ T cells, CD4+ T cells, CD8+ T cells, and neutrophils, before and after stimulation with phorbol myristate acetate, the calcium ionophore A23187, and β‐1,3‐glucan. Expression of IL‐17A transcripts and protein were determined using nCounter and ultra‐sensitive Simoa technology, respectively. MAIT cells from the axial entheses of non‐axial SpA control patients (n = 5) were further characterized using flow cytometric immunophenotyping and quantitative polymerase chain reaction, and the production of IL‐17 was assessed following stimulation.    Results  On a per‐cell basis, MAIT cells from peripheral blood produced the most IL‐17A compared to CD4+ T cells ( P  < 0.01), CD8+ T cells ( P  < 0.0001), and γδ T cells ( P  < 0.0001). IL‐17A was not produced by neutrophils. Gene expression analysis also revealed significantly higher expression of  IL17A  and  IL23R  in MAIT cells. Stimulation of peripheral blood MAIT cells with anti‐CD3/CD28 and IL‐7 and/or IL‐18 induced strong expression of  IL17F . MAIT cells were present in the normal, unaffected entheses of control patients who did not have axial SpA and showed elevated  AHR ,  JAK1 ,  STAT4 , and  TGFB1  transcript expression with inducible IL‐17A protein. IL‐18 protein expression was evident in spinal enthesis digests.    Conclusion  Both peripheral blood MAIT cells and resident MAIT cells in normal axial entheses contribute to the production of IL‐17 and may play important roles in the pathogenesis of axial SpA.

arthritis and rheumatology

Characterization of Blood  Mucosal‐Associated  Invariant T Cells in Patients With Axial Spondyloarthritis and of Resident  Mucosal‐Associated  Invariant T Cells From the Axial Entheses of  Non‐Axial  Spondyloarthritis Control Patients