Group 3 Innate Lymphoid Cells in Human Enthesis

Objective

Group 3 innate lymphoid cells (ILC3s) play a pivotal role in barrier tissues such as the gut and the skin, two important sites of disease in spondyloarthropathy (SpA). It was investigated whether normal and injured human enthesis, the key target tissue in early SpA, harboured ILC3s in entheseal soft tissue (EST) and adjacent peri-entheseal bone (PEB).

Methods

Interspinous ligament and spinous process bone was collected from donors with no systemic inflammatory disease, enzymatically digested and immunophenotyped. The immunological profile of entheseal cells was examined and the transcriptional profile of sorted ILC3s was compared to those isolated from SpA synovial fluid. To assess the ability of entheseal tissue to produce IL-17 and IL-22 entheseal digests were stimulated with IL-23 and IL-1β. Osteoarthritic and ruptured Achilles tissue was examined histologically.

Results

Compared to peripheral blood, human EST had a higher proportion of ILCs (p=0.008), EST and PEB both had a higher proportion of NKp44+ ILC3s (p=0.001 and p=0.043). RORγt, STAT3 and IL-23R transcript expression validated the entheseal ILC3 phenotype. Cytokine transcript expression was similar in ILC3s isolated from enthesis and SpA synovial fluid. Normal entheseal digests stimulated with IL-23/IL-1β upregulated IL17A transcript and histological examination of injured/damaged entheses showed RORγt expressing cells.

Conclusion

This work shows that human enthesis harbours a resident population of ILC3s, with the potential to participate in spondyloarthropathy pathogenesis. This article is protected by copyright. All rights reserved.