IL-10 regulates movement of intestinally-derived CD4+ T cells to the liver (46.12)

Abstract

Diseases that affect the intestine may have hepatic manifestations, but the mechanisms involved in establishing hepatic disease secondarily remain poorly understood. We previously reported that IL-10 knockout (KO) mice developed severe necrotizing hepatitis following oral infection with Trichinella spiralis. Here, we used this model of intestinal inflammation to further examine the role of IL-10 in regulating hepatic injury. Hepatic damage was induced by migrating newborn larvae (NBL). By delivering the parasite directly into the portal vein, we demonstrated that an ongoing intestinal immune response was necessary for the development of hepatitis. Intestinally-derived CD4+ cells accumulated in the livers of IL-10 KO mice, and depletion of CD4+ cells in wildtype (WT) mice led to a decrease in IL-10 production by hepatic leukocytes. Moreover, adoptive transfer of intestinally primed CD4+ T cells from IL-10 KO mice caused hepatitis in infected immunodeficient animals. Conversely, transfer of WT donor cells reduced the severity of hepatic inflammation in IL-10 KO recipients, demonstrating regulatory activity. Our results revealed that IL-10 prevented migration of intestinal T cells to the liver and inhibited the development of hepatitis. This work was supported by National Institutes of Health Grants AI 14490 (J.A.A.) and DK 67290 (S.K.B.).