iNKT cells suppress pathogenic NK1.1CD8+ T cells in DSS-induced colitis

Sung Won Lee, Hyun Jung Park, Jae Hee Cheon, Lan Wu, Luc Van Kaer, Seokmann Hong

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

T cells producing IFNγ play a pathogenic role in the development of inflammatory bowel disease (IBD). To investigate the functions of CD1d-dependent invariant natural killer T (iNKT) cells in experimental colitis induced in Yeti mice with dysregulated expression of IFNγ, we generated iNKT cell-deficient Yeti/CD1d KO mice and compared colitis among WT, CD1d KO, Yeti, and Yeti/CD1d KO mice following DSS treatment. We found that deficiency of iNKT cells exacerbated colitis and disease pathogenesis was mainly mediated by NK1.1+CD8+ T cells. Furthermore, the protective effects of iNKT cells correlated with up-regulation of regulatory T cells. Taken together, our results have demonstrated that CD1d-dependent iNKT cells and CD1d-independent NK1.1+CD8+ T cells reciprocally regulate the development of intestinal inflammatory responses mediated by IFNγ-dysregulation. These findings also identify NK1.1+CD8+ T cells as novel target cells for the development of therapeutics for human IBD.

Original languageEnglish
Article number2168
JournalFrontiers in Immunology
Volume9
Issue numberOCT
DOIs
Publication statusPublished - 2018 Oct 2

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Natural Killer T-Cells
Colitis
T-Lymphocytes
Inflammatory Bowel Diseases
Human Development
Regulatory T-Lymphocytes
Up-Regulation

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Cite this

Lee, Sung Won ; Park, Hyun Jung ; Cheon, Jae Hee ; Wu, Lan ; Van Kaer, Luc ; Hong, Seokmann. / iNKT cells suppress pathogenic NK1.1CD8+ T cells in DSS-induced colitis. In: Frontiers in Immunology. 2018 ; Vol. 9, No. OCT.
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abstract = "T cells producing IFNγ play a pathogenic role in the development of inflammatory bowel disease (IBD). To investigate the functions of CD1d-dependent invariant natural killer T (iNKT) cells in experimental colitis induced in Yeti mice with dysregulated expression of IFNγ, we generated iNKT cell-deficient Yeti/CD1d KO mice and compared colitis among WT, CD1d KO, Yeti, and Yeti/CD1d KO mice following DSS treatment. We found that deficiency of iNKT cells exacerbated colitis and disease pathogenesis was mainly mediated by NK1.1+CD8+ T cells. Furthermore, the protective effects of iNKT cells correlated with up-regulation of regulatory T cells. Taken together, our results have demonstrated that CD1d-dependent iNKT cells and CD1d-independent NK1.1+CD8+ T cells reciprocally regulate the development of intestinal inflammatory responses mediated by IFNγ-dysregulation. These findings also identify NK1.1+CD8+ T cells as novel target cells for the development of therapeutics for human IBD.",
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iNKT cells suppress pathogenic NK1.1CD8+ T cells in DSS-induced colitis. / Lee, Sung Won; Park, Hyun Jung; Cheon, Jae Hee; Wu, Lan; Van Kaer, Luc; Hong, Seokmann.

In: Frontiers in Immunology, Vol. 9, No. OCT, 2168, 02.10.2018.

Research output: Contribution to journalArticle

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