RT Journal Article
SR Electronic
T1 Impairment of intestinal intraepithelial lymphocytes in Id2 deficient mice
JF Gut
JO Gut
FD BMJ Publishing Group Ltd and British Society of Gastroenterology
SP 480
OP 486
DO 10.1136/gut.2003.022293
VO 53
IS 4
A1 J-K Kim
A1 M Takeuchi
A1 Y Yokota
YR 2004
UL http://gut.bmj.com/content/53/4/480.abstract
AB 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 CD8αβ+ T cell subsets, indicating a more pronounced effect on thymus derived IELs. Expression of αE integrin was reduced in CD4+ and CD8αβ+ 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.