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CB2 stimulation of adipose resident ILC2s orchestrates immune balance and ameliorates type 2 diabetes mellitus

Published date

July 3, 2024


"Development of type 2 diabetes mellitus (T2DM) is associated with low-grade chronic type 2 inflammation and disturbance of glucose homeostasis. Group 2 innate lymphoid cells (ILC2s) play a critical role in maintaining adipose homeostasis via the production of type 2 cytokines. Here, we demonstrate that CB2, a G-protein-coupled receptor (GPCR) and member of the endocannabinoid system, is expressed on both visceral adipose tissue (VAT)-derived murine and human ILC2s. Moreover, we utilize a combination of ex vivo and in vivo approaches to explore the functional and therapeutic impacts of CB2 engagement on VAT ILC2s in a T2DM model. Our results show that CB2 stimulation of ILC2s protects against insulin-resistance onset, ameliorates glucose tolerance, and reverses established insulin resistance. Our mechanistic studies reveal that the therapeutic effects of CB2 are mediated through activation of the AKT, ERK1/2, and CREB pathways on ILC2s. The results reveal that the CB2 agonist can serve as a candidate for the prevention and treatment of T2DM."


Pedram Shafiei-Jahani, Shi Yan, Mohammad H Kazemi, Xin Li, Amitis Akbari, Kei Sakano, Yoshihiro Sakano, Benjamin P Hurrell, Omid Akbari


CB2, CP: Immunology, CP: Metabolism, ILC2, T2DM, adipose inflammation, glucose tolerance, immunotherapy, insulin resistance 

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