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Host-dependent control of early regulatory and effector T-cell differentiation underlies the genetic susceptibility of RAG2-deficient mouse strains to transfer colitis.
MedLine Citation:
PMID:  23149660     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
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.Mucosal Immunology advance online publication 14 November 2012. doi:10.1038/mi.2012.102.
Authors:
V Valatas; J He; A Rivollier; G Kolios; K Kitamura; B L Kelsall
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-11-14
Journal Detail:
Title:  Mucosal immunology     Volume:  -     ISSN:  1935-3456     ISO Abbreviation:  Mucosal Immunol     Publication Date:  2012 Nov 
Date Detail:
Created Date:  2012-11-14     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101299742     Medline TA:  Mucosal Immunol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Department of Gastroenterology, Heraklion University Hospital, Heraklion, Crete, Greece.
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