GPR84 is an inflammation-induced receptor highly expressed on immune cells, yet its endogenous ligand is still unknown. This makes any interpretation of its physiological activity in vivo difficult. However, experiments with potent synthetic agonists have highlighted what the receptor can do, namely, enhance proinflammatory signaling and macrophage effector functions such as phagocytosis. Developing drugs to block these effects has attracted interest from the scientific community with the aim of decreasing disease activity in inflammatory disorders or enhancing inflammation resolution. In this review, we critically reassess the widely held belief that the major role of GPR84 is that of being a medium-chain fatty acid (MCFA) receptor. While MCFAs have been shown to activate GPR84, it remains to be demonstrated that they are present in relevant tissues at appropriate concentrations. In contrast to four other “full-time” free fatty acid receptor subtypes, GPR84 is not expressed by enteroendocrine cells and has limited expression in the gastrointestinal tract. Across multiple tissues and cell types, the highest expression levels of GPR84 are observed hours after exposure to an inflammatory stimulus. These factors obscure the relationship between ligand and receptor in the human body and do not support the exclusive physiological pairing of MCFAs with GPR84. To maximize the chances of developing efficacious drugs for inflammatory diseases, we must advance our understanding of GPR84 and what it does in vivo.

中文翻译：

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孤儿20年：GPR84是否是可能的中链脂肪酸敏感受体？

GPR84是在免疫细胞上高度表达的炎症诱导受体，但其内源配体仍然未知。这可以解释其体内的生理活性难。然而，使用有效的合成激动剂进行的实验强调了受体的作用，即增强促炎信号传导和巨噬细胞效应功能，例如吞噬作用。为了减少炎症性疾病的疾病活动或增强炎症消退的目的，开发可阻断这些作用的药物引起了科学界的关注。在这篇综述中，我们严格地重新评估了普遍认为的GPR84的主要作用是中链脂肪酸（MCFA）受体的信念。尽管已经证明MCFA可以激活GPR84，但仍有待证明它们以适当的浓度存在于相关组织中。与其他四种“全职”游离脂肪酸受体亚型不同，GPR84不由肠内分泌细胞表达，在胃肠道中的表达有限。在多种组织和细胞类型中，GPR84的最高表达水平在接触炎症刺激后数小时即可观察到。这些因素模糊了人体中配体与受体之间的关系，并不支持MCFA与GPR84的排他性生理配对。为了最大限度地开发针对炎症性疾病的有效药物的机会，我们必须加深对GPR84及其作用的理解 这些因素模糊了人体中配体与受体之间的关系，并不支持MCFA与GPR84的排他性生理配对。为了最大限度地开发针对炎症性疾病的有效药物的机会，我们必须加深对GPR84及其作用的理解 这些因素模糊了人体中配体与受体之间的关系，并不支持MCFA与GPR84的排他性生理配对。为了最大限度地开发针对炎症性疾病的有效药物的机会，我们必须加深对GPR84及其作用的理解体内。