Distinct iNKT cell populations use IFNγ or ER stress-induced IL-10 to control adipose tissue homeostasis
| Autor: | Han Dong, Ayano C. Kohlgruber, Lydia Lynch, Harry Kane, Michael B. Brenner, Nelson M. LaMarche |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Adoptive cell transfer Physiology Cell Adipose tissue Inflammation Biology Article 03 medical and health sciences Interferon-gamma Mice 0302 clinical medicine medicine Macrophage Animals Homeostasis Molecular Biology Mice Knockout Cell Biology Endoplasmic Reticulum Stress Cell biology Interleukin-10 Mice Inbred C57BL Interleukin 10 030104 developmental biology medicine.anatomical_structure Adipose Tissue Unfolded protein response Natural Killer T-Cells medicine.symptom 030217 neurology & neurosurgery |
| Zdroj: | Cell Metab Cell Metabolism |
| Popis: | 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 IFNγ. Mechanistically, biochemical fractionation revealed that free fatty acids drive IL-10 production primarily in NK1.1(NEG) iNKT cells via the IRE1α-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 IFNγ 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. |
| Databáze: | OpenAIRE |
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