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 CD8αβ⁺ T cell subsets, indicating a more pronounced effect on thymus derived IELs. Expression of α_E 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.