Neuromedin U Suppresses Collagen-Induced Arthritis through ILC2-Th2 Activation

Neuromedin U (NMU) is an evolutionarily conserved neuropeptide which was previously thought to have a proinflammatory property. Recently, it was reported that NMU induced rapid ILC2 activation and Th2 responses in allergic diseases. However, whether NMU could launch such responses in arthritis is not known. In this study, we investigated the effect of NMU administration on arthritis and its underlying mechanisms. C57BL/6 male mice were induced with collagen-induced arthritis (CIA) and treated with NMU-23 or PBS at an early stage of induction. NMU-23 dramatically inhibited clinical onset and severity of arthritis, accompanied with decreased bone erosion and number of osteoclasts. Mechanistically, NMU-23 administration induced the expansion of ILC2 and elevated eosinophil, IL-5, and IL-13 expression in the joint of arthritic mice. Although levels of Th2 cells are slightly increased, Gata3 expression level is also upregulated. Further, NMU-deficient (NMU^-/-) mice develop less severe CIA compared with control. Interestingly, the proportion of ILC2 and FoxP3⁺ regulatory T cells (Treg) was elevated in NMU^-/- mice. Taken together, our results reveal a previously unknown anti-inflammatory effect of NMU in CIA by inducing ILC2-Th2 activation.