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The link between gut and joint inflammation in spondyloarthritis (SpA) is well established, in particular in ankylosing spondylitis (AS) and peripheral SpA. In 1995, Mielants et al1 discovered that almost 50% of patients with SpA have subclinical gut inflammation, of which a fraction develops Crohn's disease over time. Recent studies clearly showed that the onset of disease and disease severity are linked to the presence of subclinical gut inflammation.2 However, the mechanism behind this phenomenon is hitherto not fully elucidated. Over the past decade, the interleukin (IL)-23/IL-17-axis has been put forward as a key player in the pathogenesis of SpA. Polymorphisms in the IL23R gene were found both in SpA and in inflammatory bowel disease (IBD),3 linking pathology in these physically distant sites. Cells that are typically responsive to IL-23 are IL-23R+RORγt+ IL-17A-producing cells, such as TH17 cells. In multiple inflammatory diseases, such as multiple sclerosis (MS), IBD and SpA, it is assumed that there is an overall distortion of the cytokine profile towards IL-17A, contributing to disease.4 However, it should be noted that in IBD IL-17A might also exert tissue-protective functions and that mechanisms driving gut inflammation in SpA do not necessarily represent those contributing to the development of full-blown IBD.3 Intriguingly, Sherlock et al5 showed that systemic IL-23 overexpression is able to drive the development of enthesitis via enthesis-resident CD3+CD4−CD8−RORγt+IL23R+ T cells, independently of TH17 cells. The concept that not TH17 cells but innate-like T cells such as γδ T cells, invariant natural killer T cells (iNKT) and mucosal-associated invariant T (MAIT) cells are the main source of IL-17A recently gained support.6
Interestingly, innate-like T cells such as MAIT cells act at the …
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