J-K Kim1, M Takeuchi, Y Yokota. 1. Department of Molecular Genetics, School of Medicine, University of Fukui, 23-3 Shimoaizuki, Matsuoka, Fukui 910-1193, Japan.
Abstract
BACKGROUND: Id2, an inhibitor of basic helix-loop-helix transcription factors, regulates cell differentiation. Id2-/- mice exhibit a variety of phenotypes in the immune system. AIMS: In this study we investigated whether Id2 plays a role in intestinal intraepithelial lymphocytes (IELs), which constitute the main defence against pathogens in the intestinal tract. METHODS: Flow cytometry and bone marrow transplantation were used to analyse and characterise subsets of IELs of Id2-/- mice. Gene expression was analysed by real-time polymerase chain reaction. Intestinal barrier function was evaluated by treating mice with 5-fluorouracil (5-FU). RESULTS: Among the four members of the Id gene family, Id2 was selectively expressed in all T cell subsets in the small intestinal IELs. Id2-/- mice showed alteration in the proportions of T cell subsets and a substantial reduction in the number of IELs, especially those of the CD4+ and CD8 alpha beta+ T cell subsets, indicating a more pronounced effect on thymus derived IELs. Expression of alphaE integrin was reduced in CD4+ and CD8 alpha beta+ T cell subsets in IELs of Id2-/- mice. IELs isolated from C57BL/6 mice reconstituted with Id2-/- bone marrow cells showed a similar phenotype to that of Id2-/- mice, indicating that the defects are intrinsic to bone marrow derived cells. Expression of genes encoding intestinal epithelial cell derived cytokines was reduced in Id2-/- mice. The 5-FU treatment revealed impaired intestinal barrier function of Id2-/- mice. CONCLUSIONS: The Id2 gene is essential for constituting the intestinal mucosal barrier, particularly with respect to IELs. Id2 null mutant mice may provide a good experimental model for studying the ontogeny of IELs and intestinal inflammation and infection.
BACKGROUND:Id2, an inhibitor of basic helix-loop-helix transcription factors, regulates cell differentiation. Id2-/- mice exhibit a variety of phenotypes in the immune system. AIMS: In this study we investigated whether Id2 plays a role in intestinal intraepithelial lymphocytes (IELs), which constitute the main defence against pathogens in the intestinal tract. METHODS: Flow cytometry and bone marrow transplantation were used to analyse and characterise subsets of IELs of Id2-/- mice. Gene expression was analysed by real-time polymerase chain reaction. Intestinal barrier function was evaluated by treating mice with 5-fluorouracil (5-FU). RESULTS: Among the four members of the Id gene family, Id2 was selectively expressed in all T cell subsets in the small intestinal IELs. Id2-/- mice showed alteration in the proportions of T cell subsets and a substantial reduction in the number of IELs, especially those of the CD4+ and CD8 alpha beta+ T cell subsets, indicating a more pronounced effect on thymus derived IELs. Expression of alphaE integrin was reduced in CD4+ and CD8 alpha beta+ T cell subsets in IELs of Id2-/- mice. IELs isolated from C57BL/6 mice reconstituted with Id2-/- bone marrow cells showed a similar phenotype to that of Id2-/- mice, indicating that the defects are intrinsic to bone marrow derived cells. Expression of genes encoding intestinal epithelial cell derived cytokines was reduced in Id2-/- mice. The 5-FU treatment revealed impaired intestinal barrier function of Id2-/- mice. CONCLUSIONS: The Id2 gene is essential for constituting the intestinal mucosal barrier, particularly with respect to IELs. Id2 null mutant mice may provide a good experimental model for studying the ontogeny of IELs and intestinal inflammation and infection.
Authors: M P Schön; A Arya; E A Murphy; C M Adams; U G Strauch; W W Agace; J Marsal; J P Donohue; H Her; D R Beier; S Olson; L Lefrancois; M B Brenner; M J Grusby; C M Parker Journal: J Immunol Date: 1999-06-01 Impact factor: 5.422
Authors: Nicholas P Semenkovich; Joseph D Planer; Philip P Ahern; Nicholas W Griffin; Charles Y Lin; Jeffrey I Gordon Journal: Proc Natl Acad Sci U S A Date: 2016-12-01 Impact factor: 11.205
Authors: Naoko Satoh-Takayama; Sarah Lesjean-Pottier; Paulo Vieira; Shinichiro Sawa; Gerard Eberl; Christian A J Vosshenrich; James P Di Santo Journal: J Exp Med Date: 2010-02-08 Impact factor: 14.307