Costimulation of type-2 innate lymphoid cells by GITR promotes effector function and ameliorates type 2 diabetes.
Lauriane Galle-TregerIshwarya SankaranarayananBenjamin P HurrellEmily HowardRichard LoHadi MaaziGavin LewisHomayon BanieAlan L EpsteinPeisheng HuVirender K RehanFrank D GillilandHooman AllayeePejman SorooshArlene H SharpeOmid AkbariPublished in: Nature communications (2019)
Metabolic syndrome is characterized by disturbances in glucose homeostasis and the development of low-grade systemic inflammation, which increase the risk to develop type 2 diabetes mellitus (T2DM). Type-2 innate lymphoid cells (ILC2s) are a recently discovered immune population secreting Th2 cytokines. While previous studies show how ILC2s can play a critical role in the regulation of metabolic homeostasis in the adipose tissue, a therapeutic target capable of modulating ILC2 activation has yet to be identified. Here, we show that GITR, a member of the TNF superfamily, is expressed on both murine and human ILC2s. Strikingly, we demonstrate that GITR engagement of activated, but not naïve, ILC2s improves glucose homeostasis, resulting in both protection against insulin resistance onset and amelioration of established insulin- resistance. Together, these results highlight the critical role of GITR as a novel therapeutic molecule against T2DM and its fundamental role as an immune checkpoint for activated ILC2s.
Keyphrases
- insulin resistance
- adipose tissue
- metabolic syndrome
- type diabetes
- low grade
- nk cells
- glycemic control
- induced apoptosis
- high fat diet
- cell cycle arrest
- blood glucose
- skeletal muscle
- high grade
- polycystic ovary syndrome
- high fat diet induced
- cardiovascular disease
- signaling pathway
- cell proliferation
- blood pressure
- dendritic cells
- cardiovascular risk factors
- type iii