ILC3 in Axial Spondyloarthritis: the Gut Angle

Abstract

Purpose of Review

A growing body of evidence supports the relevance of the interleukin-23/interleukin-17 (IL-23/IL-17) pathway for the pathogenesis of axial spondyloarthritis (axSpA) and its treatment. Recently, innate lymphoid cells (ILC), a heterogeneous family of immune effector cells, have been identified as a relevant contributor in tissue homeostasis, partially via IL-23/IL-17 axis. This review describes the biology and the origins of the group 3 ILCs (ILC3s) in humans, focusing on their role in the pathogenesis of axSpA.

Recent Findings

Clinical trials showed the effectiveness of IL23/IL-17 axis inhibition in both spondyloarthritis (SpA) and Inflammatory Bowel Disease (IBD). Recent findings confirm the high prevalence of subclinical gut inflammation in patients with SpA. Translational data in humans have demonstrated an increase in the number of ILC3s responsive to IL-23 and producing either IL-22 or IL-17 in the gut of SpA patients. The observation of gut-derived ILC3s in circulation and at inflamed tissues in patients with SpA suggest a recirculation of ILCs from mucosal site to lymphoid tissues and possibly enthesis and joints.

Summary

Multiple observations demonstrate the expansion of IL-17- and IL-22-producing ILC3 in the subclinically inflamed gut of SpA patients. These innate immune cells, also observed in normal entheses, seem to be able to re-circulate from the gut to inflamed tissues of SpA patients, thus contributing to the disease perpetuation. The development of tools that can provide access to diseased tissue from sacroiliac joint and spinal entheses will provide valuable knowledge on the role of ILC3 in axSpA pathogenesis.

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Correspondence to Francesco Ciccia.

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Mauro, D., Macaluso, F., Fasano, S. et al. ILC3 in Axial Spondyloarthritis: the Gut Angle. Curr Rheumatol Rep 21, 37 (2019). https://doi.org/10.1007/s11926-019-0834-9

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Keywords

  • Group 3 innate lymphoid cells
  • Lymphoid tissue inducer cells
  • Gut inflammation
  • Spondyloarthritis
  • Ankylosing spondylitis
  • IL-17
  • IL-23/IL-17 axis