Open AccessCostimulation of type-2 innate lymphoid cells by GITR promotes effector function and ameliorates type 2 diabetes
Author(s) -
Lauriane Galle-Treger,
Ishwarya Sankaranarayanan,
Benjamin P. Hurrell,
Emily Howard,
Richard Lo,
Hadi Maazi,
Gavin Lewis,
Homayon Banie,
Alan L. Epstein,
Peisheng Hu,
Virender K. Rehan,
Frank D. Gilliland,
Hooman Allayee,
Pejman Soroosh,
Arlene H. Sharpe,
Omid Akbari
Publication year - 2019
Publication title -
nature communications
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.559
H-Index - 365
ISSN - 2041-1723
DOI - 10.1038/s41467-019-08449-x
Subject(s) - innate lymphoid cell , immune system , immunology , insulin resistance , glucose homeostasis , homeostasis , inflammation , immunity , biology , effector , innate immune system , type 2 diabetes mellitus , population , microbiology and biotechnology , diabetes mellitus , medicine , endocrinology , environmental health
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.