title: Impairment of intestinal intraepithelial lymphocytes in Id2 deficient mice.
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.
  
  
  OBJECTIVE
  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.affiliation: Department of Molecular Genetics, School of Medicine, University of Fukui, 23-3 Shimoaizuki, Matsuoka, Fukui 910-1193, Japan.
authors.forename: J-K
authors.initials: JK
authors.lastname: Kim
authors.forename: M
authors.initials: M
authors.lastname: Takeuchi
authors.forename: Y
authors.initials: Y
authors.lastname: Yokota
mesh_terms: D000818:Animals; D018988:Bacterial Translocation / Q000187:drug effects / Q000276:immunology; D016026:Bone Marrow Transplantation / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D004847:Epithelial Cells / Q000276:immunology; D005472:Fluorouracil / Q000494:pharmacology; D015870:Gene Expression; D018257:Helix-Loop-Helix Motifs / Q000276:immunology; D018928:Immunity, Mucosal; D051797:Inhibitor of Differentiation Protein 2; D007413:Intestinal Mucosa / Q000276:immunology*; D007421:Intestine, Small / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000235:genetics; D012097:Repressor Proteins; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D014157:Transcription Factors / Q000172:deficiency / Q000235:genetics / Q000276:immunology*
chemical_list: D016207:Cytokines; D004268:DNA-Binding Proteins; C497452:Idb2 protein, mouse; D051797:Inhibitor of Differentiation Protein 2; D012333:RNA, Messenger; D012097:Repressor Proteins; D014157:Transcription Factors; D005472:Fluorouracil