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

Abstract

Abstract Type 3 innate lymphocytes have recently been reported as key factors in inflammatory diseases, but their role in viral myocarditis is unclear. By flow cytometry, coxsackievirus B3–induced myocarditis mice were detected to increase the number of type 3 innate lymphocytes, and their main type was NKp46+ type 3 innate lymphocytes. In contrast, application of CD90.2 neutralizing antibody in T-cell–deficient mice reduced the number of innate lymphocytes and improved myocarditis. Innate lymphocytes 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 coxsackievirus B3–infected recipient mice. The upregulation of S1PR1, KLF2, CXCR6, and CXCL16 in the hearts of coxsackievirus B3–infected mice, as well as the greatly reduced numbers of innate lymphocytes infiltrating the hearts after S1PR1 inhibition, suggests that intestinal innate lymphocytes may migrate to the hearts via the CXCL16/CXCR6 axis. Taken together, our results demonstrate that increased type 3 innate lymphocytes in the heart during viral myocarditis may contribute to inflammatory progression and that this increased population of type 3 innate lymphocytes likely originates from the intestine.