title: Unexpected Regulatory Role of CCR9 in Regulatory T Cell Development.
abstract: T cells reactive to microbiota regulate the pathogenesis of inflammatory bowel disease (IBD). As T cell trafficking to intestines is regulated through interactions between highly specific chemokine-chemokine receptors, efforts have been made to develop intestine-specific immunosuppression based on blocking these key processes. CCR9, a gut-trophic chemokine receptor expressed by lymphocytes and dendritic cells, has been implicated in the regulation of IBD through mediating recruitment of T cells to inflamed sites. However, the role of CCR9 in inducing and sustaining inflammation in the context of IBD is poorly understood. In this study, we demonstrate that CCR9 deficiency in effector T cells and Tregs does not affect the development of colitis in a microbiota antigen-specific, T cell-mediated model. However, Treg cells express higher levels of CCR9 compared to those in effector T cells. Interestingly, CCR9 inhibits Treg cell development, in that CCR9-/- mice demonstrate a high level of Foxp3+ Tregs, and ligation of CCR9 by its ligand CCL25 inhibits Treg cell differentiation in vitro. Collectively, our data indicate that in addition to acting as a gut-homing molecule, CCR9 signaling shapes immune responses by inhibiting Treg cell development.
authors.affiliation: Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, United States of America.
authors.forename: Heather L
authors.initials: HL
authors.lastname: Evans-Marin
authors.affiliation: Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, United States of America.
authors.forename: Anthony T
authors.initials: AT
authors.lastname: Cao
authors.affiliation: Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, United States of America.
authors.forename: Suxia
authors.initials: S
authors.lastname: Yao
authors.affiliation: Department of Pathology, University of Texas Medical Branch, Galveston, Texas, United States of America.
authors.forename: Feidi
authors.initials: F
authors.lastname: Chen
authors.affiliation: Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, United States of America; Department of Gastroenterology, The Shanghai Tenth People's Hospital, Tongji University, Shanghai, China.
authors.forename: Chong
authors.initials: C
authors.lastname: He
authors.affiliation: Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, United States of America; Department of Gastroenterology, The Qilu Hospital, Shandong University, Shandong, China.
authors.forename: Han
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, United States of America; Department of Gastroenterology, The Shanghai Tenth People's Hospital, Tongji University, Shanghai, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wu
authors.affiliation: School of Medicine, University of Texas Medical Branch, Galveston, Texas, United States of America.
authors.forename: Maria G
authors.initials: MG
authors.lastname: Gonzalez
authors.affiliation: Department of Medicine, University of Texas Medical Branch, Galveston, Texas, United States of America.
authors.forename: Sara M
authors.initials: SM
authors.lastname: Dann
authors.affiliation: Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, United States of America; Department of Pathology, University of Texas Medical Branch, Galveston, Texas, United States of America.
authors.forename: Yingzi
authors.initials: Y
authors.lastname: Cong
mesh_terms: D000818:Animals; D003092:Colitis / Q000503:physiopathology; D051379:Mice; D008822:Mice, Transgenic; D054388:Receptors, CCR / Q000235:genetics / Q000502:physiology*; D050378:T-Lymphocytes, Regulatory / Q000166:cytology*
chemical_list: C119309:CC chemokine receptor 9; D054388:Receptors, CCR