PT  - JOURNAL ARTICLE
AU  - J-K Kim
AU  - M Takeuchi
AU  - Y Yokota
TI  - Impairment of intestinal intraepithelial lymphocytes in Id2 deficient mice
AID  - 10.1136/gut.2003.022293
DP  - 2004 Apr 01
TA  - Gut
PG  - 480--486
VI  - 53
IP  - 4
4099  - http://gut.bmj.com/content/53/4/480.short
4100  - http://gut.bmj.com/content/53/4/480.full
SO  - Gut2004 Apr 01; 53
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.