Memory/effector (CD45RBlo) CD4 T cells are controlled directly by IL-10 and cause IL-22–dependent intestinal pathology

摘要

The role of direct IL-10 signaling in different T cell subsets is not well understood. To address this, we generated transgenic mice expressing a dominant-negative IL-10 receptor specifically in T cells (CD4dnIL-10Rα). We found that Foxp3-depleted CD45RB^lo (regulatory T cell [Treg cell]–depleted CD45RB^lo) but not CD45RB^hi CD4⁺ T cells are controlled directly by IL-10 upon transfer into Rag1 knockout (KO) mice. Furthermore, the colitis induced by transfer of Treg cell–depleted CD45RB^lo CD4⁺ T cells into Rag1 KO mice was characterized by reduced Th1 and increased Th17 cytokine messenger RNA levels in the colon as compared with the colitis induced by transfer of CD45RB^hi T cells. In contrast to the CD45RB^hi transfer colitis model, in which IL-22 is protective, we found that T cell–derived IL-22 was pathogenic upon transfer of Treg cell–depleted CD45RB^lo T cells into Rag1 KO mice. Our results highlight characteristic differences between colitis induced by naive (CD45RB^hi) and memory/effector (Treg cell–depleted CD45RB^lo) cells and different ways that IL-22 impacts inflammatory bowel disease.