IL-23 Responsive innate-like T cells in spondyloarthritis: the less frequent they are, the more vital they appear

A key role for the IL-23/IL-17 immune axis in spondyloarthritis (SpA) is supported by cumulative evidence from genetic and translational studies and was recently confirmed in clinical trials. Although initially linked to T helper 17 cells, it is now clear that additional unconventional T cell subpopulations respond towards IL-23, including ROR gamma t(+) CD3(+)CD4(-)CD8(-) T cells, TCR gamma delta 17 cells, KIR3DL2(+)CD4(+) T cells and iNKT17 cells. Although these innate-like T cells are present only at low frequencies and often with a specific tissue distribution, it is proposed that they could play a vital function in the development or progression of SpA-related pathology. In this review, we highlight the emerging knowledge on these specialized IL-23 responsive T cells with regard to their relevance in SpA. Finally, we will discuss these findings in light of novel drugs targeting the IL-23/IL-17 axis, currently being tested in SpA patients

Ankylosing spondylitis: an autoimmune or autoinflammatory disease?

Ankylosing spondylitis (AS) is a chronic inflammatory disorder of unknown aetiology. Unlike other systemic autoimmune diseases, in AS, the innate immune system has a dominant role characterized by aberrant activity of innate and innate-like immune cells, including γδ T cells, group 3 innate lymphoid cells, neutrophils, mucosal-associated invariant T cells and mast cells, at sites predisposed to the disease. The intestine is involved in disease manifestations, as it is at the forefront of the interaction between the mucosal-associated immune cells and the intestinal microbiota. Similarly, biomechanical factors, such as entheseal micro-trauma, might also be involved in the pathogenesis of the articular manifestation of AS, and sentinel immune cells located in the entheses could provide links between local damage, genetic predisposition and the development of chronic inflammation. Although these elements might support the autoinflammatory nature of AS, studies demonstrating the presence of autoantibodies (such as anti-CD74, anti-sclerostin and anti-noggin antibodies) and evidence of activation and clonal expansion of T cell populations support an autoimmune component to the disease. This Review presents the evidence for autoinflammation and the evidence for autoimmunity in AS and, by discussing the pathophysiological factors associated with each, aims to reconcile the two hypotheses.</p