Memory/effector (CD45RB ^lo) CD4 T cells are controlled directly by IL-10 and cause IL-22–dependent intestinal pathology

Abstract

Interleukin-10 acts directly on CD45RB ^lo but not CD45RB ^hi cells to control colitis upon transfer into Rag1-deficient recipients.

Abstract

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 [T _reg 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 T _reg 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 T _reg 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 (T _reg cell–depleted CD45RB ^lo) cells and different ways that IL-22 impacts inflammatory bowel disease.