期刊
CELLULAR & MOLECULAR IMMUNOLOGY
卷 19, 期 2, 页码 260-275出版社
CHIN SOCIETY IMMUNOLOGY
DOI: 10.1038/s41423-021-00812-7
关键词
Dendritic Cells; NKT; Obesity; ageing; FLT3L
类别
资金
- Spanish Ministerio de Ciencia, Innovacion (MICINN)
- Agencia Estatal de Investigacion (AEI)
- Fondo Europeo de Desarrollo Regional (FEDER) [RTI2018-094484-B-I00, RYC-2016-19463]
- FPI fellowship from the Spanish Ministry of Science and Innovation [PRE2019-087509]
- European Research Council [725091]
- MICINN
- FEDER [PID2019-108157RB]
- Comunidad de Madrid [IMMUNOTHERCAN-CM S2010/BMD-2326, B2017/BMD-3733 Immunothercan-CM, B2017/BMD-3733]
- Fundacio La Marato de TV3 [201723]
- European Union [ERC 260464]
- EFSD/Lilly European Diabetes Research Programme GS
- 2017 Leonardo Grant for Researchers and Cultural Creators
- MINECO-FEDER [SAF2016-79126-R]
- Fundacion AECC
- EFSD/Lilly
- Instituto de Salud Carlos III (ISCIII)
- Pro CNIC Foundation
- JdC-Incorporation [IJC2018-035390-I]
- EFSD Rising star
- BBVA Foundation [IN[17]_BBM_BAS_0066]
- AEI
- [EUIN2017-85875]
- European Research Council (ERC) [725091] Funding Source: European Research Council (ERC)
Conventional dendritic cells type 1 (cDC1s) play a critical role in adipose tissue homeostasis, with a connection to NK1.1(+) invariant NKT (iNKT) cells, and have an impact on adipose tissue inflammation and overall metabolic health.
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-gamma 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.
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