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Front. Immunol. | doi: 10.3389/fimmu.2018.02168

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

Sung Won Lee1, Hyun Jung Park1, Jae Hee Cheon2, Lan Wu3,  Luc Van Kaer3* and  Seokmann Hong1*
  • 1Sejong University, South Korea
  • 2Yonsei University College of Medicine, South Korea
  • 3School of Medicine, Vanderbilt University, United States

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.

Keywords: CD1d-dependent NKT cells, NK1.1+CD8+ T cells, Treg cells, IFNγ, DSS-induced colitis

Received: 14 Jun 2018; Accepted: 03 Sep 2018.

Edited by:

Yun-Cai Liu, Tsinghua University, China

Reviewed by:

Koji Yasutomo, Tokushima University, Japan
Hiroshi Watarai, Institute of Medical Science, University of Tokyo, Japan  

Copyright: © 2018 Lee, Park, Cheon, Wu, Van Kaer and Hong. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Prof. Luc Van Kaer, School of Medicine, Vanderbilt University, Nashville, 37232, Tennessee, United States, luc.van.kaer@vanderbilt.edu
Prof. Seokmann Hong, Sejong University, Seoul, South Korea, shong@sejong.ac.kr