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Impairment of intestinal intraepithelial lymphocytes in Id2 deficient mice
  1. J-K Kim,
  2. M Takeuchi,
  3. Y Yokota
  1. Department of Molecular Genetics, School of Medicine, University of Fukui, 23-3 Shimoaizuki, Matsuoka, Fukui 910-1193, Japan
  1. Correspondence to:
    Professor Y Yokota
    Department of Molecular Genetics, School of Medicine, University of Fukui, 23-3 Shimoaizuki, Matsuoka, Fukui 910-1193, Japan; yyokotafmsrsa.fukui-med.ac.jp

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 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.

  • Id2 mice
  • intestinal intraepithelial lymphocytes
  • lamina propria lymphocytes
  • mucosal immunity
  • small intestine
  • 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-β, transforming growth factor β
  • IFN-γ, interferon γ
  • 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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