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oai:repisalud.isciii.es:20.500.12105/150982025-04-01T10:22:00Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605

00925njm 22002777a 4500 dc Hernández-García, Elena author Cueto, Francisco J author Cook, Emma CL author Redondo-Urzainqui, Ana author Charro-Zanca, Sara author Robles-Vera, Iñaki author Conde-Garrosa, Ruth author Nikolić, Ivana author Sabio, Guadalupe author Sancho, David author Iborra, Salvador author 2022-02 Conventional dendritic cells (cDCs) scan and integrate environmental cues in almost every tissue, including exogenous metabolic signals. While cDCs are critical in maintaining immune balance, their role in preserving energy homeostasis is unclear. Here, we showed that Batf3-deficient mice lacking conventional type 1 DCs (cDC1s) had increased body weight and adiposity during aging. This led to impaired energy expenditure and glucose tolerance, insulin resistance, dyslipidemia, and liver steatosis. cDC1 deficiency caused adipose tissue inflammation that was preceded by a paucity of NK1.1+ invariant NKT (iNKT) cells. Accordingly, among antigen-presenting cells, cDC1s exhibited notable induction of IFN-γ production by iNKT cells, which plays a metabolically protective role in lean adipose tissue. Flt3L treatment, which expands the dendritic cell (DC) compartment, mitigated diet-induced obesity and hyperlipidemia in a Batf3-dependent manner. This effect was partially mediated by NK1.1+ cells. These results reveal a new critical role for the cDC1-iNKT cell axis in the regulation of adipose tissue homeostasis. Cellular & Molecular Immunology volume 19, pages260–275 (2022) http://hdl.handle.net/20.500.12105/15098 34983945 10.1038/s41423-021-00812-7 2042-0226 Cellular & molecular immunology Conventional type 1 dendritic cells protect against age-related adipose tissue dysfunction and obesity.