摘要
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-γproduction 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.
基金
Work in the S.I.laboratory is funded by the Spanish Ministerio de Ciencia,Innovación(MICINN),Agencia Estatal de Investigación(AEI)and Fondo Europeo de Desarrollo Regional(FEDER),RTI2018-094484-BI00,and RYC-2016-19463.EHG is the recipient of an FPI fellowship(PRE2019-087509)from the Spanish Ministry of Science and Innovation.Work in the DS laboratory is funded by the CNIC
the European Research Council(ERC-2016-Consolidator Grant 725091)
the MICINN,AEI and FEDER(PID2019-108157RB)
Comunidad de Madrid(B2017/BMD-3733 Immunothercan-CM)
Atresmedia(Constantes y Vitales prize)
and FundacióLa Maratóde TV3(201723).Work in the G.S.laboratory receives funding from the European Union’s Seventh Framework Programme(FP7/2007-2013)under grant agreement n°ERC 260464,EFSD/Lilly European Diabetes Research Programme GS,2017 Leonardo Grant for Researchers and Cultural Creators,BBVA Foundation(Investigadores-BBVA-2017)IN[17]_BBM_BAS_0066,MINECO-FEDER SAF2016-79126-R,EUIN2017-85875,Comunidad de Madrid IMMUNOTHERCAN-CM S2010/BMD-2326 and B2017/BMD-3733 and Fundación AECC.IN receives funding from EFSD/Lilly(2019),EFSD Rising star(2019),and JdC-Incorporation(IJC2018-035390-I)
The CNIC is supported by the Instituto de Salud Carlos III(ISCIII),the MICINN,and the Pro CNIC Foundation。
