GPR84 regulates pulmonary inflammation by modulating neutrophil functions

Wang, Siwei; Zhang, Qing; Lu, Dan; Fang, You‐Chen; Yan, Xiao-Ci; Chen, Jing; Xia, Zhi-Kan; Yuan, Qianting; Chen, Linhai; Zhang, Yangming; Xie, Xin

doi:10.1038/s41401-023-01080-z

Cited by 17 publications

(6 citation statements)

References 63 publications

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“…LPS, a cell wall component of Gram-negative bacteria, is found in various occupational dusts and air pollutants, and its elevated concentration causes high expression of various cytokines and chemokines in the human body, ultimately leading to the formation and aggravation of pneumonia. , To investigate the immunoinhibitory effect of MSC-EVs-PD-L1, we used LPS to induce ARDS in mice − (Figure a). DiD-labeled MSC-EVs-PD-L1 were intratracheally injected into ARDS mice.…”

Section: Resultsmentioning

confidence: 99%

PD-L1-Expressing Extracellular Vesicles for the Treatment of Pneumonia

Wu,

Wang,

Song

et al. 2023

ACS Biomater. Sci. Eng.

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Acute respiratory distress syndrome (ARDS) is a severe lung condition with a high mortality rate and a lack of effective drug therapy. In this work, we developed mesenchymal stem cell (MSC)-derived extracellular vesicles with high PD-L1 expression (MSC-EVs-PD-L1) for treating lipopolysaccharide (LPS)-induced pneumonia by intratracheal administration. We found an upregulation of PD-1 expression in the inflammatory region of murine lungs; hence, MSC-EVs-PD-L1 exerted immunosuppressive effects via the PD-1/PD-L1 signaling pathway. Furthermore, we treated LPS-induced pneumonia mice by intratracheal administration, which enabled heavy drug accumulation in the lungs of mice and better therapeutic efficacy compared to systemic administration. Our results suggest that MSC-EVs-PD-L1 has the potential to provide a universal platform technology for the immunotherapy of pneumonia.

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Section: Resultsmentioning

confidence: 99%

PD-L1-Expressing Extracellular Vesicles for the Treatment of Pneumonia

Wu,

Wang,

Song

et al. 2023

ACS Biomater. Sci. Eng.

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“…After dewaxing and hydration, HE staining was performed with hematoxylin and eosin, after which the sections were dehydrated and sealed under a microscope. Pathological analysis was performed according to Smith’s semiquantitative lung injury pathological scoring criteria as detailed in previous studies ( Smith et al., 1997 ; Wang et al., 2023 ).…”

Section: Methodsmentioning

confidence: 99%

Gut microbes improve prognosis of Klebsiella pneumoniae pulmonary infection through the lung-gut axis

Tang,

Chen,

Yang

et al. 2024

Front. Cell. Infect. Microbiol.

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BackgroundThe gut microbiota plays a vital role in the development of sepsis and in protecting against pneumonia. Previous studies have demonstrated the existence of the gut-lung axis and the interaction between the gut and the lung, which is related to the prognosis of critically ill patients; however, most of these studies focused on chronic lung diseases and influenza virus infections. The purpose of this study was to investigate the effect of faecal microbiota transplantation (FMT) on Klebsiella pneumoniae-related pulmonary infection via the gut-lung axis and to compare the effects of FMT with those of traditional antibiotics to identify new therapeutic strategies.MethodsWe divided the mice into six groups: the blank control (PBS), pneumonia-derived sepsis (KP), pneumonia-derived sepsis + antibiotic (KP + PIP), pneumonia-derived sepsis + faecal microbiota transplantation(KP + FMT), antibiotic treatment control (KP+PIP+PBS), and pneumonia-derived sepsis+ antibiotic + faecal microbiota transplantation (KP + PIP + FMT) groups to compare the survival of mice, lung injury, inflammation response, airway barrier function and the intestinal flora, metabolites and drug resistance genes in each group.ResultsAlterations in specific intestinal flora can occur in the gut of patients with pneumonia-derived sepsis caused by Klebsiella pneumoniae. Compared with those in the faecal microbiota transplantation group, the antibiotic treatment group had lower levels of proinflammatory factors and higher levels of anti-inflammatory factors but less amelioration of lung pathology and improvement of airway epithelial barrier function. Additionally, the increase in opportunistic pathogens and drug resistance-related genes in the gut of mice was accompanied by decreased production of favourable fatty acids such as acetic acid, propionic acid, butyric acid, decanoic acid, and secondary bile acids such as chenodeoxycholic acid 3-sulfate, isodeoxycholic acid, taurodeoxycholic acid, and 3-dehydrocholic acid; the levels of these metabolites were restored by faecal microbiota transplantation. Faecal microbiota transplantation after antibiotic treatment can gradually ameliorate gut microbiota disorder caused by antibiotic treatment and reduce the number of drug resistance genes induced by antibiotics.ConclusionIn contrast to direct antibiotic treatment, faecal microbiota transplantation improves the prognosis of mice with pneumonia-derived sepsis caused by Klebsiella pneumoniae by improving the structure of the intestinal flora and increasing the level of beneficial metabolites, fatty acids and secondary bile acids, thereby reducing systemic inflammation, repairing the barrier function of alveolar epithelial cells, and alleviating pathological damage to the lungs. The combination of antibiotics with faecal microbiota transplantation significantly alleviates intestinal microbiota disorder, reduces the selection for drug resistance genes caused by antibiotics, and mitigates lung lesions; these effects are superior to those following antibiotic monotherapy.

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“…Further studies found that the activation of GPR84 strongly induced neutrophils to produce ROS by stimulating the activation of Lyn, AKT and ERK1/2 and the assembly of NADPH oxidase. The lack or blockage of GPR84 can significantly improve the pulmonary inflammation of ALI mice by reducing neutrophil infiltration and oxidative stress [ 62 ].…”

Section: The Impact Of Free Fatty Acids Uptake and Transportation On Alimentioning

confidence: 99%

The role of fatty acid metabolism in acute lung injury: a special focus on immunometabolism

Lu,

Li,

Liu

et al. 2024

Cell. Mol. Life Sci.

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Reputable evidence from multiple studies suggests that excessive and uncontrolled inflammation plays an indispensable role in mediating, amplifying, and protracting acute lung injury (ALI). Traditionally, immunity and energy metabolism are regarded as separate functions regulated by distinct mechanisms, but recently, more and more evidence show that immunity and energy metabolism exhibit a strong interaction which has given rise to an emerging field of immunometabolism. Mammalian lungs are organs with active fatty acid metabolism, however, during ALI, inflammation and oxidative stress lead to a series metabolic reprogramming such as impaired fatty acid oxidation, increased expression of proteins involved in fatty acid uptake and transport, enhanced synthesis of fatty acids, and accumulation of lipid droplets. In addition, obesity represents a significant risk factor for ALI/ARDS. Thus, we have further elucidated the mechanisms of obesity exacerbating ALI from the perspective of fatty acid metabolism. To sum up, this paper presents a systematical review of the relationship between extensive fatty acid metabolic pathways and acute lung injury and summarizes recent advances in understanding the involvement of fatty acid metabolism-related pathways in ALI. We hold an optimistic believe that targeting fatty acid metabolism pathway is a promising lung protection strategy, but the specific regulatory mechanisms are way too complex, necessitating further extensive and in-depth investigations in future studies.

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GPR84 regulates pulmonary inflammation by modulating neutrophil functions

Cited by 17 publications

References 63 publications

PD-L1-Expressing Extracellular Vesicles for the Treatment of Pneumonia

PD-L1-Expressing Extracellular Vesicles for the Treatment of Pneumonia

Gut microbes improve prognosis of Klebsiella pneumoniae pulmonary infection through the lung-gut axis

The role of fatty acid metabolism in acute lung injury: a special focus on immunometabolism

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