| First Author | Fu Z | Year | 2021 |
| Journal | Nat Commun | Volume | 12 |
| Issue | 1 | Pages | 4462 |
| PubMed ID | 34294718 | Mgi Jnum | J:321203 |
| Mgi Id | MGI:6741386 | Doi | 10.1038/s41467-021-24755-9 |
| Citation | Fu Z, et al. (2021) Mitochondrial transcription factor A in RORgammat(+) lymphocytes regulate small intestine homeostasis and metabolism. Nat Commun 12(1):4462 |
| abstractText | RORgammat(+) lymphocytes, including interleukin 17 (IL-17)-producing gamma delta T (gammadeltaT17) cells, T helper 17 (Th17) cells, and group 3 innate lymphoid cells (ILC3s), are important immune regulators. Compared to Th17 cells and ILC3s, gammadeltaT17 cell metabolism and its role in tissue homeostasis remains poorly understood. Here, we report that the tissue milieu shapes splenic and intestinal gammadeltaT17 cell gene signatures. Conditional deletion of mitochondrial transcription factor A (Tfam) in RORgammat(+) lymphocytes significantly affects systemic gammadeltaT17 cell maintenance and reduces ILC3s without affecting Th17 cells in the gut. In vivo deletion of Tfam in RORgammat(+) lymphocytes, especially in gammadeltaT17 cells, results in small intestine tissue remodeling and increases small intestine length by enhancing the type 2 immune responses in mice. Moreover, these mice show dysregulation of the small intestine transcriptome and metabolism with less body weight but enhanced anti-helminth immunity. IL-22, a cytokine produced by RORgammat(+) lymphocytes inhibits IL-13-induced tuft cell differentiation in vitro, and suppresses the tuft cell-type 2 immune circuit and small intestine lengthening in vivo, highlighting its key role in gut tissue remodeling. |
