GPR81, a Cell-Surface Receptor for Lactate, Regulates Intestinal Homeostasis and Protects Mice from Experimental Colitis

Ranganathan, Punithavathi; Shanmugam, Arul; Swafford, Daniel; Suryawanshi, Amol; Bhattacharjee, Pushpak; Hussein, Mohamed S.; Koni, Pandelakis A.; Prasad, Puttur D.; Kurago, Zoya B.; Thangaraju, Muthusamy; Ganapathy, Vadivel; Manicassamy, Santhakumar

doi:10.4049/jimmunol.1700604

Cited by 112 publications

(119 citation statements)

References 59 publications

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“…Lactate is carried across cell membranes by a class of transmembrane proteins known as MCTs [also known as solute carrier 16 (SLC16)], which cotransport protons and lactate anions down the concentration gradients of the lactate anion and proton (22). MCTs constitute a family of 14 transporters, and the most common types are MCT1 (SLC16A1) and MCT4 (SLC16A3) (23).…”

Section: Monocarboxylic Acid Transporters (Mcts)mentioning

confidence: 99%

Lactic Acid: A Novel Signaling Molecule in Early Pregnancy?

Huang

Muyayalo

et al. 2020

Front. Immunol.

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Aerobic glycolysis is a recognized feature shared by tumors, leading to the accumulation of lactic acid in their local microenvironments. Like the tumors, the blastocysts, placenta, trophoblasts and decidual immune cells can also produce a large amount of lactic acid through aerobic glycolysis during the early pregnancy. Moreover, the placenta expresses the transporters of the lactic acid. While several studies have described the role of lactic acid in the tumor microenvironment, especially lactic acid's modulation of immune cells, the role of lactic acid produced during pregnancy is still unclear. In this paper, we reviewed the scientific evidence detailing the effects of lactic acid in the tumor microenvironment. Based on the influence of the lactic acid on immune cells and tumors, we proposed that lactic acid released in the unique uterine environment could have similar effects on the trophoblast cells and immune cells during the early pregnancy.

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Section: Monocarboxylic Acid Transporters (Mcts)mentioning

confidence: 99%

Lactic Acid: A Novel Signaling Molecule in Early Pregnancy?

Huang

Muyayalo

et al. 2020

Front. Immunol.

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“…Supplementation of lactate or pyruvate enhanced uptake and immune responses to S. typhimurium infection, which was not afforded in Gpr31 -/mice. Engagement of lactate with its other receptor, Gpr81, on intestinal dendritic cells and macrophages was also shown to reduce colitis by suppressing cytokine production and Th1/Th17 cell differentiation [84], but whether this was due to gut microbegenerated lactate in particular was not addressed.…”

Section: Effect Of Commensal Metabolites On Host Immune Functionmentioning

confidence: 99%

Metabolism at the centre of the host–microbe relationship

Maslowski

2019

Clinical and Experimental Immunology

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Summary Maintaining homoeostatic host–microbe interactions is vital for host immune function. The gut microbiota shapes the host immune system and the immune system reciprocally shapes and modifies the gut microbiota. However, our understanding of how these microbes are tolerated and how individual, or communities of, gut microbes influence host function is limited. This review will focus on metabolites as key mediators of this complex host–microbe relationship. It will look at the central role of epithelial metabolism in shaping the gut microbiota, how microbial metabolites influence the epithelium and the mucosal and peripheral immune system, and how the immune system shapes microbial composition and metabolism. Finally, this review will look at how metabolites are involved in cross‐talk between different members of the microbiota and their role during infections.

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“…In situ hybridization showed that GPR81 is located at astrocytic end-feet membranes, endothelial cell membranes, and highly at neuronal synaptic membranes (K. H. Lauritzen et al, 2014). Furthermore, the expression of GPR81 is also found in macrophage cells (Hoque et al, 2014), uterus (A. Madaan et al, 2017), and the antigen-presenting cells (APCs) and other immune cells of the intestine (Ranganathan et al, 2018).…”

Section: The Discovery Tissue Distribution and Expression Of Gpr81mentioning

confidence: 99%

The roles of GRP81 as a metabolic sensor and inflammatory mediator

Cai

Liu

et al. 2020

Journal Cellular Physiology

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GPR81 (also named as HCA1) is a member of a subfamily of orphan G‐protein coupled receptors (GPCRs), coupled to Gi‐type G proteins. GPR81 was discovered in 2001 and identified as the only known endogenous receptor of lactate under physiological conditions in 2008, which opened a new field of research on how lactate may act as a signal molecule along with the GPR81 expression in the roles of metabolic process and inflammatory response. Recent studies showed that the physiological functions of GPR81 include lipid metabolism in adipose tissues, metabolic excitability in the brain, cellular development, and inflammatory response modulation. These findings may reveal a novel therapeutic strategy to treat clinical, metabolic, and inflammatory diseases. This article will summarize past research on GPR81, including its characteristics of distribution and expression, functional residues, pharmacological, and physiological agonists, involvement in signal transduction, and pharmacological applications.

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GPR81, a Cell-Surface Receptor for Lactate, Regulates Intestinal Homeostasis and Protects Mice from Experimental Colitis

Cited by 112 publications

References 59 publications

Lactic Acid: A Novel Signaling Molecule in Early Pregnancy?

Lactic Acid: A Novel Signaling Molecule in Early Pregnancy?

Metabolism at the centre of the host–microbe relationship

The roles of GRP81 as a metabolic sensor and inflammatory mediator

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