title: Host-dependent control of early regulatory and effector T-cell differentiation underlies the genetic susceptibility of RAG2-deficient mouse strains to transfer colitis.
abstract: De novo differentiation of CD4(+)Foxp3(+) regulatory T cells (induced (i) Tregs) occurs preferentially in the gut-associated lymphoid tissues (GALT). We addressed the contribution of background genetic factors in affecting the balance of iTreg, T helper type 1 (Th1), and Th17 cell differentiation in GALT in vivo following the transfer of naive CD4(+)CD45RB(high) T cells to strains of RAG2-deficient mice with differential susceptibility to inflammatory colitis. iTregs represented up to 5% of CD4(+) T cells in mesenteric lymph nodes of less-susceptible C57BL/6 RAG2(-/-) mice compared with <1% in highly susceptible C57BL/10 RAG2(-/-) mice 2 weeks following T-cell transfer before the onset of colitis. Early Treg induction was correlated inversely with effector cell expansion and the severity of colitis development, was controlled primarily by host and not T-cell-dependent factors, and was strongly associated with interleukin-12 (IL-12)/23 production by host CD11c(+)CD103(+) dendritic cells. These data highlight the importance of genetic factors regulating IL-12/23 production in controlling the balance between iTreg differentiation and effector-pathogenic CD4(+) T-cell expansion in lymphopenic mice and indicate a direct role for iTregs in the regulation of colonic inflammation in vivo.
authors.affiliation: Department of Gastroenterology, Heraklion University Hospital, Heraklion, Crete, Greece.
authors.forename: V
authors.initials: V
authors.lastname: Valatas
authors.forename: J
authors.initials: J
authors.lastname: He
authors.forename: A
authors.initials: A
authors.lastname: Rivollier
authors.forename: G
authors.initials: G
authors.lastname: Kolios
authors.forename: K
authors.initials: K
authors.lastname: Kitamura
authors.forename: B L
authors.initials: BL
authors.lastname: Kelsall
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D015704:CD4 Antigens / Q000378:metabolism; D002454:Cell Differentiation; D002478:Cells, Cultured; D003092:Colitis / Q000276:immunology*; D004268:DNA-Binding Proteins / Q000172:deficiency*; D003713:Dendritic Cells / Q000276:immunology*; D051858:Forkhead Transcription Factors; D020022:Genetic Predisposition to Disease; D018664:Interleukin-12 / Q000378:metabolism; D053759:Interleukin-23 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D013045:Species Specificity; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000637:transplantation; D018417:Th1 Cells / Q000276:immunology* / Q000637:transplantation; D058504:Th17 Cells / Q000276:immunology* / Q000637:transplantation
chemical_list: D015704:CD4 Antigens; D004268:DNA-Binding Proteins; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D053759:Interleukin-23; C064655:V(D)J recombination activating protein 2; D018664:Interleukin-12