| First Author | LaMarche NM | Year | 2020 |
| Journal | Cell Metab | Volume | 32 |
| Issue | 2 | Pages | 243-258.e6 |
| PubMed ID | 32516575 | Mgi Jnum | J:296581 |
| Mgi Id | MGI:6469028 | Doi | 10.1016/j.cmet.2020.05.017 |
| Citation | LaMarche NM, et al. (2020) Distinct iNKT Cell Populations Use IFNgamma or ER Stress-Induced IL-10 to Control Adipose Tissue Homeostasis. Cell Metab 32(2):243-258.e6 |
| abstractText | Adipose tissue invariant natural killer T (iNKT) cells are phenotypically different from other iNKT cells because they produce IL-10 and control metabolic homeostasis. Why that is the case is unclear. Here, using single-cell RNA sequencing, we found several adipose iNKT clusters, which we grouped into two functional populations based on NK1.1 expression. NK1.1(NEG) cells almost exclusively produced IL-10 and other regulatory cytokines, while NK1.1(POS) iNKT cells predominantly produced IFNgamma. Mechanistically, biochemical fractionation revealed that free fatty acids drive IL-10 production primarily in NK1.1(NEG) iNKT cells via the IRE1alpha-XBP1s arm of the unfolded protein response. Correspondingly, adoptive transfer of adipose tissue NK1.1(NEG) iNKT cells selectively restored metabolic function in obese mice. Further, we found an unexpected role for NK1.1(POS) iNKT cells in lean adipose tissue, as IFNgamma licenses natural killer cell-mediated macrophage killing to limit pathological macrophage expansion. Together, these two iNKT cell populations utilize non-redundant pathways to preserve metabolic integrity. |
