小柯机器人

美国约翰霍普金斯大学Xinzhong Dong课题组发现，GPCR-神经肽轴通过促进细菌感染期间的一种替代性极化，来抑制嗜中性粒细胞的过度活跃。该研究于2024年1月30日发表于国际一流学术期刊《免疫》杂志上。

研究人员证明了中性粒细胞表达的G蛋白偶联受体（GPCR）Mrgpra1是中性粒细胞杀菌功能的负调控因子。Mrgpra1介导的信号由其配体神经肽FF（NPFF）驱动，后者决定了促炎和抗炎程序之间的平衡。具体来说，在急性肺部感染期间，Mrgpra1-NPFF轴通过偏向于替代性极化来反调节干扰素（IFN）γ介导的中性粒细胞极化，这表明它可能起到平衡过度狂热的中性粒细胞反应的作用。

在感染过程中，不同的、交叉调节的中性粒细胞群是NPFF和IFNγ的主要来源。由于处于稳定状态的中性粒细胞中有一部分表达NPFF，这些发现可能对各种感染性和炎症性疾病有广泛的影响。因此，中性粒细胞的内在途径决定了它们的细胞命运、功能和感染程度。

研究人员表示，中性粒细胞作为一个同质群体存在的观念正在被中性粒细胞具有不同功能状态的知识所取代。中性粒细胞可以具有促炎表型或抗炎状态，但这些状态是如何调节的仍不清楚。

附：英文原文

Title: A GPCR-neuropeptide axis dampens hyperactive neutrophils by promoting an alternative-like polarization during bacterial infection

Author: Naina Gour, Hwan Mee Yong, Aishwarya Magesh, Aishwarya Atakkatan, Felipe Andrade, Stephane Lajoie, Xinzhong Dong

Issue&Volume: 2024-01-30

Abstract: The notion that neutrophils exist as a homogeneous population is being replaced with the knowledge that neutrophils adopt different functional states. Neutrophils can have a pro-inflammatory phenotype or an anti-inflammatory state, but how these states are regulated remains unclear. Here, we demonstrated that the neutrophil-expressed G-protein-coupled receptor (GPCR) Mrgpra1 is a negative regulator of neutrophil bactericidal functions. Mrgpra1-mediated signaling was driven by its ligand, neuropeptide FF (NPFF), which dictated the balance between pro- and anti-inflammatory programming. Specifically, the Mrgpra1-NPFF axis counter-regulated interferon (IFN) γ-mediated neutrophil polarization during acute lung infection by favoring an alternative-like polarization, suggesting that it may act to balance overzealous neutrophilic responses. Distinct, cross-regulated populations of neutrophils were the primary source of NPFF and IFNγ during infection. As a subset of neutrophils at steady state expressed NPFF, these findings could have broad implications in various infectious and inflammatory diseases. Therefore, a neutrophil-intrinsic pathway determines their cellular fate, function, and magnitude of infection.

DOI: 10.1016/j.immuni.2024.01.003

Source: https://www.cell.com/immunity/fulltext/S1074-7613(24)00028-1

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