S1PR1-dependent migration of ILC3s from intestinal tissue to the heart in a mouse model of viral myocarditis.

Abstract

Type 3 innate lymphocytes (ILC3s) have recently been reported as key factors in inflammatory diseases, however, their role in viral myocarditis is unclear. By flow cytometry, CVB3 (Coxsachievirus B3)-induced myocarditis mice were detected to increase the number of ILC3s, and their main type was NKp46 + ILC3. In contrast, application of CD90.2 neutralizing antibody in T-cell-deficient mice reduced the number of ILCs and improved myocarditis. ILCs from CD45.1 mouse intestinal lamina propria lymphocytes were adoptively transferred into recipient mice, and a comparable proportion of CD45.1+ cells were observed in the hearts of CVB3-infected recipient mice. The upregulation of S1PR1 (Recombinant Sphingosine 1 Phosphate Receptor 1), KLF2 (Kruppel-like factor 2), CXCR6, and CXCL16 in the hearts of CVB3-infected mice, as well as the greatly reduced numbers of ILCs infiltrating the hearts after S1PR1 inhibition, suggest that intestinal ILCs may migrate to the hearts via the CXCL16/CXCR6 axis. Taken together, our results demonstrate that increased ILC3 in the heart during viral myocarditis may contribute to inflammatory progression, and that this increased population of ILC3 likely originates from the intestine.