caa a22 4500 445797452 CHVBK 20180317145130.0 cr unu---uuuuu 170323e20110201xx s 000 0 eng 10.1007/s10620-010-1286-2 doi (NATIONALLICENCE)springer-10.1007/s10620-010-1286-2 CD4+CD25+ Regulatory T Cells Suppress Th17-Responses in an Experimental Colitis Model [Elektronische Daten] [Haruei Ogino, Kazuhiko Nakamura, Eikich Ihara, Hirotada Akiho, Ryoichi Takayanagi] Background: After the recent discovery of Th17 cells, it was proposed that Th17 responses are involved in the pathogenesis of inflammatory bowel diseases (IBD). CD4+CD25+ regulatory T cells (Treg) are considered to be an attractive tool for the treatment of IBD. Here, we investigated whether Treg are capable of suppressing Th17-mediated colitis. Methods: Naive CD4+ T cells were transferred into SCID mice with or without Treg. In some experiments, Treg were transferred into recipient mice with established colitis. Mice treated with Treg were injected with an anti-transforming growth factor (TGF)-β mAb or control IgG. Clinical symptoms of colitis, histological changes and cytokine expressions were investigated. Results: SCID mice transferred with naive CD4+ T cells developed chronic colitis with significant increases in Th1 and Th17 cytokine expressions in the colon. When Treg were co-transferred with naive CD4+ T cells, development of colitis was prevented, and Th17 cytokine expressions were markedly reduced. Similarly, when Treg were transferred into mice with established colitis, the colitis was significantly ameliorated in association with dramatic reductions in Th17 cytokine expressions. Injection of anti-TGF-β mAb abolished the Treg-mediated suppression with significant elevations in Th17 cytokine productions. Conclusion: This adoptive transfer model of colitis was associated with augmented Th1 and Th17 responses, and Treg were capable of suppressing colonic inflammation by downregulating Th17 responses as well as Th1 responses via TGF-β. Consequently, Treg transfer therapy is expected to be efficacious for IBD even if Th17 is involved in the pathogenesis. Springer Science+Business Media, LLC, 2010 Colitis model nationallicence Inflammatory bowel diseases nationallicence Regulatory T cells nationallicence T helper 17 cells nationallicence Transforming growth factor-β nationallicence Ogino Haruei Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, 812-8582, Higashi-ku, Fukuoka, Japan aut Nakamura Kazuhiko Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, 812-8582, Higashi-ku, Fukuoka, Japan aut Ihara Eikich Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, 812-8582, Higashi-ku, Fukuoka, Japan aut Akiho Hirotada Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, 812-8582, Higashi-ku, Fukuoka, Japan aut Takayanagi Ryoichi Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, 812-8582, Higashi-ku, Fukuoka, Japan aut Digestive Diseases and Sciences Springer US; http://www.springer-ny.com 56/2(2011-02-01), 376-386 0163-2116 56:2<376 2011 56 10620 https://doi.org/10.1007/s10620-010-1286-2 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s10620-010-1286-2 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Ogino Haruei Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, 812-8582, Higashi-ku, Fukuoka, Japan aut NATIONALLICENCE 700 1- Nakamura Kazuhiko Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, 812-8582, Higashi-ku, Fukuoka, Japan aut NATIONALLICENCE 700 1- Ihara Eikich Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, 812-8582, Higashi-ku, Fukuoka, Japan aut NATIONALLICENCE 700 1- Akiho Hirotada Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, 812-8582, Higashi-ku, Fukuoka, Japan aut NATIONALLICENCE 700 1- Takayanagi Ryoichi Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, 812-8582, Higashi-ku, Fukuoka, Japan aut NATIONALLICENCE 773 0- Digestive Diseases and Sciences Springer US; http://www.springer-ny.com 56/2(2011-02-01), 376-386 0163-2116 56:2<376 2011 56 10620 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer