INTESTINAL IMMUNOLOGY

Impairment of intestinal intraepithelial lymphocytes in Id2 deficient mice

J-K Kim, M Takeuchi, Y Yokota

Department of Molecular Genetics, School of Medicine, University of Fukui, 23-3 Shimoaizuki, Matsuoka, Fukui 910-1193, Japan

Correspondence to:
Correspondence to:
Professor Y Yokota
Department of Molecular Genetics, School of Medicine, University of Fukui, 23-3 Shimoaizuki, Matsuoka, Fukui 910-1193, Japan; yyokota{at}fmsrsa.fukui-med.ac.jp

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 CD8ß⁺ T cell subsets, indicating a more pronounced effect on thymus derived IELs. Expression of _E integrin was reduced in CD4⁺ and CD8ß⁺ 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.

Keywords: Id2 mice; intestinal intraepithelial lymphocytes; lamina propria lymphocytes; mucosal immunity; small intestine

Abbreviations: bHLH, basic helix-loop-helix; IELs, intestinal intraepithelial lymphocytes; LPLs, lamina propria lymphocytes; IECs, intestinal epithelial cells; RT-PCR, reverse transcription-polymerase chain reaction; TCR, T cell receptor; IL, interleukin; TGF-ß, transforming growth factor ß; IFN-, interferon ; FCS, fetal calf serum; PBS, phosphate buffered saline; FITC, fluorescein isothiocyanate; PE, phycoerythrin; mAb, monoclonal antibody; 5-FU, 5-fluorouracil; SCF, stem cell factor

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