Glucose-dependent insulinotropic polypeptide (GIP) is an incretin hormone traditionally known for its insulinotropic and adipogenic effects. However, its role in immune modulation and inflammation has Show more
Glucose-dependent insulinotropic polypeptide (GIP) is an incretin hormone traditionally known for its insulinotropic and adipogenic effects. However, its role in immune modulation and inflammation has recently gained attention, particularly in the context of metabolic diseases. By conducting a comprehensive search into the scientific literature since the discovery of GIP hormone, this review examines the biological evidences linking GIP and inflammation in pre-clinical and clinical studies. Pharmacological approaches targeting the GIP receptor (GIPR) with effects on inflammatory processes are discussed as well, including the latest GIP-based multi-target approaches. The impact of GIP on inflammation appears context-dependent and influenced by tissue-specific receptor expression and metabolic status. While GIP has been shown to exert both pro- and anti-inflammatory effects in experimental models, clinical data are still limited. The success of GIP/glucagon-like peptide-1 (GLP-1) dual agonists in improving glycometabolic and inflammatory outcomes, highlighted the need to disentangle the individual contributions of each pathway. GIPR remains a promising, yet understudied, target in immunometabolism. Future studies are needed to clarify the molecular mechanisms underpinning GIP’s immunomodulatory actions and evaluate the anti-inflammatory potential of GIP-targeting therapies in clinical settings. Show less
Multiple sclerosis (MS) is more prevalent in women, with a female-to-male ratio of 3:1. The molecular mechanisms driving this sex difference are still mostly unknown. MS results from immune dysfunctio Show more
Multiple sclerosis (MS) is more prevalent in women, with a female-to-male ratio of 3:1. The molecular mechanisms driving this sex difference are still mostly unknown. MS results from immune dysfunction, with an imbalance in effector and regulatory T cells. Among the latter, Type I regulatory T cells (Tr1) are dysfunctional in people with MS (pwMS), secreting less IL-10, a potent anti-inflammatory cytokine, than in healthy donors. Our objectives were to explore the effect of biological sex on Tr1 cell differentiation in healthy donors and pwMS. CD4 We found that healthy female Tr1 cells produce less IL-10 than male cells (16 women and 16 men, 18-45 years old, We demonstrate that sex influences IL-10 production by Tr1 cells via the PI3K pathway, potentially contributing to the greater susceptibility of women to MS. Furthermore, our data suggest that targeting PI3Kδ may represent a novel therapeutic strategy to boost IL-10 production in female pwMS. Show less