| First Author | Park HJ | Year | 2021 |
| Journal | Int J Mol Sci | Volume | 22 |
| Issue | 3 | PubMed ID | 33513946 |
| Mgi Jnum | J:338626 | Mgi Id | MGI:7506746 |
| Doi | 10.3390/ijms22031250 | Citation | Park HJ, et al. (2021) CD1d-Dependent iNKT Cells Control DSS-Induced Colitis in a Mouse Model of IFNgamma-Mediated Hyperinflammation by Increasing IL22-Secreting ILC3 Cells. Int J Mol Sci 22(3) |
| abstractText | We have previously shown that CD1d-restricted iNKT cells suppress dysregulated IFNgamma expression and intestinal inflammation in Yeti mice on the C57BL/6 background. Since type 3 innate lymphoid cells (ILC3s) in mesenteric lymph nodes (MLN) protect against intestinal inflammation in a CD1d-associated manner, we investigated whether crosstalk between iNKT cells and MLN ILC3s controls IFNgamma-mediated intestinal inflammation in Yeti mice. We found that Yeti mice display increased levels of ILC3s and that iNKT cell deficiency in Yeti/CD1d KO mice decreases levels of IL22-producing ILC3s during DSS-induced colitis. This finding indicates that iNKT cells and ILC3s cooperate to regulate intestinal inflammation in Yeti mice. Yeti iNKT cells displayed a pronounced anti-inflammatory (IL4- or IL9-producing) phenotype during colitis. Their adoptive transfer to iNKT cell-deficient animals induced a significant increase in IL22 production by ILC3s, indicating that crosstalk between iNKT cells and ILC3s plays a critical role in modulating colitis in Yeti mice. Moreover, we showed that the IL9-producing subset of iNKT cells potently enhances IL22-producing ILC3s in vivo. Taken together, our results identify a central role of the iNKT cell-ILC3 axis in ameliorating IFNgamma-mediated intestinal inflammation. |
