First Author | Kim JK | Year | 2004 |
Journal | Gut | Volume | 53 |
Issue | 4 | Pages | 480-6 |
PubMed ID | 15016739 | Mgi Jnum | J:102067 |
Mgi Id | MGI:3606555 | Doi | 10.1136/gut.2003.022293 |
Citation | Kim JK, et al. (2004) Impairment of intestinal intraepithelial lymphocytes in Id2 deficient mice. Gut 53(4):480-6 |
abstractText | 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. |