1. Memory/effector (CD45RB(lo)) CD4 T cells are controlled directly by IL-10 and cause IL-22-dependent intestinal pathology.
- Author
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Kamanaka M, Huber S, Zenewicz LA, Gagliani N, Rathinam C, O'Connor W Jr, Wan YY, Nakae S, Iwakura Y, Hao L, and Flavell RA
- Subjects
- Animals, Colitis genetics, Colitis metabolism, Colitis pathology, Colon immunology, Colon metabolism, Colon pathology, Homeodomain Proteins immunology, Homeodomain Proteins metabolism, Humans, Inflammatory Bowel Diseases genetics, Inflammatory Bowel Diseases metabolism, Inflammatory Bowel Diseases pathology, Interleukin-10 genetics, Interleukin-10 metabolism, Interleukins genetics, Interleukins metabolism, Leukocyte Common Antigens genetics, Leukocyte Common Antigens metabolism, Mice, Mice, Knockout, T-Lymphocytes, Regulatory metabolism, T-Lymphocytes, Regulatory pathology, Th17 Cells immunology, Th17 Cells metabolism, Th17 Cells pathology, Interleukin-22, Colitis immunology, Immunologic Memory, Inflammatory Bowel Diseases immunology, Interleukin-10 immunology, Interleukins immunology, Leukocyte Common Antigens immunology, T-Lymphocytes, Regulatory immunology
- 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.
- Published
- 2011
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