title: Memory/effector (CD45RB(lo)) CD4 T cells are controlled directly by IL-10 and cause IL-22-dependent intestinal pathology.
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.
authors.affiliation: Department of Immunobiology, School of Medicine, Yale University, New Haven, CT 06520, USA.
authors.forename: Masahito
authors.initials: M
authors.lastname: Kamanaka
authors.forename: Samuel
authors.initials: S
authors.lastname: Huber
authors.forename: Lauren A
authors.initials: LA
authors.lastname: Zenewicz
authors.forename: Nicola
authors.initials: N
authors.lastname: Gagliani
authors.forename: Chozhavendan
authors.initials: C
authors.lastname: Rathinam
authors.forename: William
authors.initials: W
authors.lastname: O'Connor
authors.forename: Yisong Y
authors.initials: YY
authors.lastname: Wan
authors.forename: Susumu
authors.initials: S
authors.lastname: Nakae
authors.forename: Yoichiro
authors.initials: Y
authors.lastname: Iwakura
authors.forename: Liming
authors.initials: L
authors.lastname: Hao
authors.forename: Richard A
authors.initials: RA
authors.lastname: Flavell
mesh_terms: D000818:Animals; D003092:Colitis / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D003106:Colon / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D018398:Homeodomain Proteins / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007156:Immunologic Memory; D015212:Inflammatory Bowel Diseases / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D016753:Interleukin-10 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D007378:Interleukins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D017493:Leukocyte Common Antigens / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D058504:Th17 Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D000097043:Interleukin-22
chemical_list: D018398:Homeodomain Proteins; D016753:Interleukin-10; D007378:Interleukins; D017493:Leukocyte Common Antigens; D000097043:Interleukin-22; C508609:IL10 protein, human; C556062:IL10 protein, mouse; C064658:RAG-1 protein