iNKT Cells Suppress Pathogenic NK1.1+CD8+ T Cells in DSS-Induced Colitis
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-defic...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2018-10-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2018.02168/full |
| _version_ | 1818198575206629376 |
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| author | Sung Won Lee Hyun Jung Park Jae Hee Cheon Lan Wu Luc Van Kaer Seokmann Hong |
| author_facet | Sung Won Lee Hyun Jung Park Jae Hee Cheon Lan Wu Luc Van Kaer Seokmann Hong |
| author_sort | Sung Won Lee |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-12T02:08:03Z |
| format | Article |
| id | doaj.art-fc72d924012e49d2b61313f0d727d1c9 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-12T02:08:03Z |
| publishDate | 2018-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-fc72d924012e49d2b61313f0d727d1c92022-12-22T00:41:59ZengFrontiers Media S.A.Frontiers in Immunology1664-32242018-10-01910.3389/fimmu.2018.02168408109iNKT Cells Suppress Pathogenic NK1.1+CD8+ T Cells in DSS-Induced ColitisSung Won Lee0Hyun Jung Park1Jae Hee Cheon2Lan Wu3Luc Van Kaer4Seokmann Hong5Department of Integrative Bioscience and Biotechnology, Institute of Anticancer Medicine Development, Sejong University, Seoul, South KoreaDepartment of Integrative Bioscience and Biotechnology, Institute of Anticancer Medicine Development, Sejong University, Seoul, South KoreaDepartment of Internal Medicine and Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, South KoreaDepartment of Pathology, Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, TN, United StatesDepartment of Pathology, Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, TN, United StatesDepartment of Integrative Bioscience and Biotechnology, Institute of Anticancer Medicine Development, Sejong University, Seoul, South KoreaT 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.https://www.frontiersin.org/article/10.3389/fimmu.2018.02168/fullCD1d-dependent NKT cellsNK1.1+CD8+ T cellsTreg cellsIFNγDSS-induced colitis |
| spellingShingle | Sung Won Lee Hyun Jung Park Jae Hee Cheon Lan Wu Luc Van Kaer Seokmann Hong iNKT Cells Suppress Pathogenic NK1.1+CD8+ T Cells in DSS-Induced Colitis Frontiers in Immunology CD1d-dependent NKT cells NK1.1+CD8+ T cells Treg cells IFNγ DSS-induced colitis |
| title | iNKT Cells Suppress Pathogenic NK1.1+CD8+ T Cells in DSS-Induced Colitis |
| title_full | iNKT Cells Suppress Pathogenic NK1.1+CD8+ T Cells in DSS-Induced Colitis |
| title_fullStr | iNKT Cells Suppress Pathogenic NK1.1+CD8+ T Cells in DSS-Induced Colitis |
| title_full_unstemmed | iNKT Cells Suppress Pathogenic NK1.1+CD8+ T Cells in DSS-Induced Colitis |
| title_short | iNKT Cells Suppress Pathogenic NK1.1+CD8+ T Cells in DSS-Induced Colitis |
| title_sort | inkt cells suppress pathogenic nk1 1 cd8 t cells in dss induced colitis |
| topic | CD1d-dependent NKT cells NK1.1+CD8+ T cells Treg cells IFNγ DSS-induced colitis |
| url | https://www.frontiersin.org/article/10.3389/fimmu.2018.02168/full |
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