IL-22- and GM-CSF-expressing but not IL-17A-expressing group 3 innate lymphoid cells are expanded in the inflamed spondyloarthritis joint.

OBJECTIVE: Clinical trials of the anti-IL-17A antibody secukinumab demonstrated a crucial role of the IL-17A cytokine in the pathogenesis of spondyloarthritis (SpA), however its cellular source in this condition remains controversial. Group 3 innate lymphoid cells (ILC3s) have been recently identified in a number of different tissues as potent producers of proinflamatory cytokines, including IL-17A and IL-22. In this study we set out to characterize the presence and composition of ILCs and investigate whether these cells are an important source of IL-17A in the synovial tissue of patients with SpA.

METHODS: Matched synovial tissue (ST), synovial fluid (SF) and peripheral blood (PB) were obtained from SpA patients with actively inflamed knee joints. ILC subsets were characterised by flow cytometry. Gene expression analysis at the single-cell level was performed directly ex vivo and after in vitro activation.. IL-17A ELISPOT assay was used to detect IL-17A-secreting cells.

RESULTS: Analysis revealed that ILCs, and particularly NKp44-positive ILC3s, are expanded in inflamed arthritic joints. Single-cell expression analysis demonstrated that ST ILCs are clearly distinguishable from ST T cells and from their PB counterparts. We detected expression of Th17 signature transcripts RORC, AHR and IL-23R in a large fraction of ST ILC3s. These cells were capable to induce IL-22 and CSF2 but not IL-17A expression in response to in vitro re-stimulation.

CONCLUSIONS: We demonstrate that ILC3s are absolutely and relatively enriched in the synovial joint of patients with SpA, however these cells are not a significant source of IL-17A cytokine in this pathology. This article is protected by copyright. All rights reserved.