Search

Insights into the relationship between immunometabolism and inflammation have enabled the targeting of several immunity-mediated inflammatory processes that underlie infectious diseases and cancer or drive transplant rejection, but this field remains largely unexplored in kidney diseases. The kidneys comprise heterogeneous cell populations, contain distinct microenvironments such as areas of hypoxia and hypersalinity, and are responsible for a functional triad of filtration, reabsorption and secretion. These distinctive features create myriad potential metabolic therapeutic targets in the kidney. Immune cells have crucial roles in the maintenance of kidney homeostasis and in the response to kidney injury, and their function is intricately connected to their metabolic properties. Changes in nutrient availability and biomolecules, such as cytokines, growth factors and hormones, initiate cellular signalling events that involve energy-sensing molecules and other metabolism-related proteins to coordinate immune cell differentiation, activation and function. Disruption of homeostasis promptly triggers the metabolic reorganization of kidney immune and non-immune cells, which can promote inflammation and tissue damage. The metabolic differences between kidney and immune cells offer an opportunity to specifically target immunometabolism in the kidney. [ABSTRACT FROM AUTHOR]

Cardiorenal syndrome type 3 (CRS 3) occurs when there is an acute kidney injury (AKI) leading to the development of an acute cardiac injury. The immune system is involved in modulating the severity of kidney injury, and the role of immune system cells in the development of CRS 3 is not well established. The present work aims to characterize the macrophage and T and B lymphocyte populations in kidney and heart tissue after AKI induced by renal I/R. Thus, C57BL/6 mice were subjected to a renal I/R protocol by occlusion of the left renal pedicle (unilateral) for 60 min, followed by reperfusion for 3, 8 and 15 days. The immune cell populations of interest were identified using flow cytometry, and RT-qPCR was used to evaluate gene expression. As a result, a significant increase in TCD4+, TCD8+ lymphocytes and M1 macrophages to the renal tissue was observed, while B cells in the heart decreased. A renal tissue repair response characterized by Foxp3 activation predominated. However, a more inflammatory profile was shown in the heart tissue influenced by IL-17RA and IL-1β. In conclusion, the AKI generated by renal I/R was able to activate and recruit T and B lymphocytes and macrophages, as well as pro-inflammatory mediators to renal and cardiac tissue, showing the role of the immune system as a bridge between both organs in the context of CRS 3. [ABSTRACT FROM AUTHOR]

Intestinal epithelial cells constantly crosstalk with the gut microbiota and immune cells of the gut lamina propria. Enteroendocrine cells, secrete hormones, such as incretin hormones, which participate in host physiological events, such as stimulating insulin secretion, satiety, and glucose homeostasis. Interestingly, evidence suggests that the incretin pathway may influence immune cell activation. Consequently, drugs targeting the incretin hormone signaling pathway may ameliorate inflammatory diseases such as inflammatory bowel diseases, cancer, and autoimmune diseases. In this review, we discuss how these hormones may modulate two subsets of CD4 + T cells, the regulatory T cells (Treg)/Th17 axis important for gut homeostasis: thus, preventing the development and progression of inflammatory diseases. We also summarize the main experimental and clinical findings using drugs targeting the glucose‐dependent insulinotropic polypeptide (GIP) and glucagon‐like peptide (GLP-1) signaling pathways and their great impact on conditions in which the Treg/Th17 axis is disturbed such as inflammatory diseases and cancer. Understanding the role of incretin stimulation in immune cell activation and function, might contribute to new therapeutic designs for the treatment of inflammatory diseases, autoimmunity, and tumors. • CD26 blockade by vildagliptin decreased IL-17 production. • Bone marrow recipient animals from GIPR-/- donors have a decrease in Treg cells. • GLP-1 analogue (liraglutide) decreased Th17 cells and increased Treg. • Colitis-inducing mice treated with sitagliptin reduce disease status. • GLP-1R agonist (Ex-4) increased Treg population and reduce T1D. [ABSTRACT FROM AUTHOR]