Acute respiratory distress syndrome (ARDS) is a kind of comprehensive disease with excessive inflammation and high clinical mortality. Multiple immune cells are involved in the ARDS process. Amongst these populations, lung-resident alveolar macrophages (AMs) are known to participate in the regulation of ARDS. GPR84, a metabolite-sensing GPCR sensing medium-chain fatty acids (MCFAs), is highly expressed in LPS-challenged macrophages and considered as a pro-inflammatory receptor. In this study, it was hypothesized that Gpr84 may be involved in pulmonary homeostasis via its regulatory effect on the switch of AM status. In LPS-induced ALI mouse model, we identified the internal LPS-induced switch of AMs from CD11b^lo to more inflamed CD11b^hi status, which is deeply related to the exacerbated imbalance of homeostasis in the lung injury process. Gpr84 was highly expressed in ALI lung tissues and involved in cytokine release, phagocytosis and status switch of AMs through positive regulatory crosstalk with TLR4-related pathways via CD14 and LBP, which relied on Akt, Erk1/2, and STAT3. If conserved in humans, GPR84 may represent a potential therapeutic target for ARDS.

急性呼吸窘迫综合征（ARDS）是一种炎症过度、临床死亡率高的综合性疾病。多种免疫细胞参与 ARDS 过程。在这些人群中，肺部肺泡巨噬细胞 (AM) 已知参与 ARDS 的调节。GPR84 是一种代谢物感应 GPCR 感应中链脂肪酸 (MCFA)，在 LPS 攻击的巨噬细胞中高表达，被认为是促炎受体。在这项研究中，假设Gpr84可能通过其对 AM 状态转换的调节作用参与肺稳态。在 LPS 诱导的 ALI 小鼠模型中，我们确定了内部 LPS 诱导的 AMs 从 CD11b ^lo转换为更发炎的 CD11b ^hi状态，这与肺损伤过程中体内平衡失衡的加剧密切相关。Gpr84在 ALI 肺组织中高表达，并通过依赖于 Akt、Erk1/2 和 STAT3 的 CD14 和 LBP 与 TLR4 相关通路的正调控串扰参与 AMs 的细胞因子释放、吞噬作用和状态转换。如果在人类中保守，GPR84 可能代表 ARDS 的潜在治疗靶点。