title: Competition between colitogenic Th1 and Th17 cells contributes to the amelioration of colitis.
abstract: Th17 cells and Th1 cells coordinate to play a critical role in the formation of inflammatory bowel diseases. To examine how Th17 and Th1 cells are regulated at inflammatory sites, we used Th1-dominant CD4(+)CD45RB(high) T cell-transferred RAG-2(-/-) and Th1/Th17-mixed IL-10(-/-) mice. Interestingly, not only did colitic RAG-2(-/-) mice that were parabiosed with WT mice show significant amelioration of colitis, but amelioration of disease was also observed in those parabiosed with colitic IL-10(-/-) mice. To assess the interference between Th1 and Th17 colitogenic T cells, we co-transferred colitogenic CD4(+) T cells from the lamina propria (LP) of CD4(+)CD45RB(high) T cell-transferred RAG-2(-/-) mice and IL-10(-/-) mice into RAG-2(-/-) mice. Surprisingly, the co-transferred RAG-2(-/-) mice showed a vast cellular infiltration of LP CD4(+) T cells similar to that seen in RAG-2(-/-) mice re-transferred with the cells from colitic RAG-2(-/-) mice alone, but the co-transferred RAG-2(-/-) mice did not have the wasting symptoms, which are also absent in RAG-2(-/-) mice transferred with cells from colitic IL-10(-/-) mice alone. Furthermore, the percentages of Th1 and Th17 cells originating from IL-10(-/-) mice and those of Th1 cells originating from colitic RAG-2(-/-) mice were all significantly decreased in the co-transferred mice as compared with the singly-transferred paired RAG-2(-/-) mice, suggesting that Th1 and Th17 cells are in competition, and that their orchestration results in a merged clinical phenotype of the two types of murine colitis.
authors: Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan.
authors: Yohei
authors: Y
authors: Mikami
authors: Takanori
authors: T
authors: Kanai
authors: Tomohisa
authors: T
authors: Sujino
authors: Yuichi
authors: Y
authors: Ono
authors: Atsushi
authors: A
authors: Hayashi
authors: Akira
authors: A
authors: Okazawa
authors: Nobuhiko
authors: N
authors: Kamada
authors: Katsuyoshi
authors: K
authors: Matsuoka
authors: Tadakazu
authors: T
authors: Hisamatsu
authors: Susumu
authors: S
authors: Okamoto
authors: Hiromasa
authors: H
authors: Takaishi
authors: Nagamu
authors: N
authors: Inoue
authors: Haruhiko
authors: H
authors: Ogata
authors: Toshifumi
authors: T
authors: Hibi
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D015704:CD4 Antigens / Q000096:biosynthesis; D002450:Cell Communication / Q000276:immunology; D003092:Colitis / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D004268:DNA-Binding Proteins / Q000235:genetics; D004195:Disease Models, Animal; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000276:immunology*; D016753:Interleukin-10 / Q000235:genetics; D020381:Interleukin-17 / Q000378:metabolism; D017493:Leukocyte Common Antigens / Q000096:biosynthesis; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009092:Mucous Membrane / Q000276:immunology* / Q000473:pathology; D010227:Parabiosis; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism* / Q000473:pathology
chemical_list: D015704:CD4 Antigens; D004268:DNA-Binding Proteins; D020381:Interleukin-17; C499308:Rag2 protein, mouse; D016753:Interleukin-10; D017493:Leukocyte Common Antigens