Innate Lymphoid Cells Type 2 Attenuate Inflammatory Arthritis and Protect from Bone Destruction

Abstract

Innate lymphoid cells 2 (ILC2) is a new immune cell lineage described in parasite defense and allergic inflammation. ILC2 were detected in the peripheral blood and the joints of rheumatoid arthritis (RA) patients, serum-induced arthritis (SIA) and collagen-induced arthritis (CIA) using flow cytometry. To elucidate the role of ILC2 in arthritis loss of function (RORαcre/GATA3fl/fl mice) and gain of function models (IL-25/IL-33 minicircles, IL-2/IL-2 antibody complex, ILC2 adoptive transfer) for ILC2 were subjected to arthritis. Circulating ILC2s were significantly increased in RA compared to healthy controls and inversely correlated with disease activity. Induction of arthritis in mice led to fast increase in IL-4&#43ILC2 numbers. Loss of ILC2 function in RORαcre/GATA3fl/fl mice significantly exacerbated arthritis. While the induction of IL-4&#43ILC2 in mice by IL-25/IL33 mini-circles or IL-2/IL-2 antibody complex and the adoptive transfer of ILC2 significantly attenuated arthritis. These data show that ILC2s have immune-regulatory functions in arthritis.