Group 3 innate lymphoid cells promotes Th17 cells differentiation in rheumatoid arthritis.

Objectives: To investigate the correlation between innate lymphoid cell (ILC) subsets with T-helper (Th) cells and to explore the effect of ILCs on T cells in rheumatoid arthritis (RA).

Methods: We analysed the frequencies of ILC subsets in RA patients with varying disease activity and their correlation with Th cell subsets. We further investigated this correlation in various organs of collagen-induced arthritis (CIA) mice. The effects of ILCs on CD4+ T cells were determined by in vitro cell co-culture experiments.

Results: ILCs were less frequent in RA patients than in healthy controls, with higher levels of group 3 ILCs (ILC3s) in RA (p<0.05). ILC3s correlated positively with Th1 and Th17 cells in RA peripheral blood (p<0.05). In the peripheral blood, spleen, and lymph nodes of CIA, ILC3s decreased and then increased during arthritis progression. ILC3s correlated positively with Th1 and Th17 cells in the spleen and lymph nodes of CIA (p<0.05). NKp46+ ILC3s in the spleen positively correlated with Th1 and Th17 cells (p<0.05). Under Th17 cell differentiation conditions, co-culturing CIA-derived ILC3s directly with naive CD4+ T cells promoted Th17 differentiation and increased IL-17 secretion. However, co-culturing through a transwell insert impeded Th17 differentiation without affecting IL-17 secretion.

Conclusions: ILC3s positively correlated with Th1 and Th17 cells in RA. In CIA, the frequencies of ILC3s changed with disease development and showed a positive correlation with Th1 and Th17 cells. ILC3s may facilitate the differentiation of Th17 cells through direct cell-cell contact.