title: T regulatory cells maintain intestinal homeostasis by suppressing γδ T cells.
abstract: Immune tolerance against enteric commensal bacteria is important for preventing intestinal inflammation. Deletion of phosphoinositide-dependent protein kinase 1 (Pdk1) in T cells via Cd4-Cre induced chronic inflammation of the intestine despite the importance of PDK1 in T cell activation. Analysis of colonic intraepithelial lymphocytes of PDK1-deficient mice revealed markedly increased CD8α(+) T cell receptor (TCR)γδ(+) T cells, including an interleukin-17 (IL-17)-expressing population. TCRγδ(+) T cells were responsible for the inflammatory colitis as shown by the fact that deletion of Tcrd abolished spontaneous colitis in the PDK1-deficient mice. This dysregulation of intestinal TCRγδ(+) T cells was attributable to a reduction in the number and functional capacity of PDK1-deficient T regulatory (Treg) cells. Adoptive transfer of wild-type Treg cells abrogated the spontaneous activation and proliferation of intestinal TCRγδ(+) T cells observed in PDK1-deficient mice and prevented the development of colitis. Therefore, suppression of intestinal TCRγδ(+) T cells by Treg cells maintains enteric immune tolerance.
authors.affiliation: Department of Microbiology & Immunology, Columbia University, College of Physicians & Surgeons, New York, NY 10032, USA.
authors.forename: Sung-Gyoo
authors.initials: SG
authors.lastname: Park
authors.forename: Ramkumar
authors.initials: R
authors.lastname: Mathur
authors.forename: Meixiao
authors.initials: M
authors.lastname: Long
authors.forename: Namiko
authors.initials: N
authors.lastname: Hosh
authors.forename: Liming
authors.initials: L
authors.lastname: Hao
authors.forename: Matthew S
authors.initials: MS
authors.lastname: Hayden
authors.forename: Sankar
authors.initials: S
authors.lastname: Ghosh
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D016827:CD8 Antigens / Q000276:immunology; D003092:Colitis / Q000201:enzymology / Q000209:etiology / Q000276:immunology; D006706:Homeostasis / Q000276:immunology*; D007108:Immune Tolerance; D020381:Interleukin-17 / Q000276:immunology; D007422:Intestines / Q000201:enzymology / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000201:enzymology / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000201:enzymology / Q000276:immunology*
chemical_list: D016827:CD8 Antigens; C409469:CD8 antigen, alpha chain; D020381:Interleukin-17; C000631433:Pdk1 protein, mouse; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase; D016692:Receptors, Antigen, T-Cell, gamma-delta; D017346:Protein Serine-Threonine Kinases