MiR‐144‐induced KLF2 inhibition and NF‐kappaB/CXCR1 activation promote neutrophil extracellular trap–induced transfusion‐related acute lung injury

Le, Aiping; Wu, Yize; Liu, Wei; Wu, Chenggao; Hu, Piao-Ping; Zou, Juan; Kuang, Linju

doi:10.1111/jcmm.16650

Cited by 15 publications

(10 citation statements)

References 44 publications

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“…Accumulating evidence has suggested that miR-144-3p expression is deeply tied with immune responses in various diseases. − Here, miR-144-3p was found to be upregulated in H37Ra-infected macrophages (RAW264.7 cells and BMDMs), line with earlier findings suggesting the miR-144-3p induction as exposed to BCG or nontuberculous mycobacteria challenge. , Furthermore, compared to healthy people, TB patients had higher miR-144-3p expression in their serum and sputum . These results indicate that miR-144-3p may be crucial in Mtb infection.…”

Section: Discussionsupporting

confidence: 87%

MicroRNA-144-3p Inhibits Host Lipid Catabolism and Autophagy by Targeting PPARα and ABCA1 During Mycobacterium Tuberculosis Infection

Wu,

Zhang,

Tang

et al. 2024

ACS Infect. Dis.

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MicroRNA-mediated metabolic reprogramming recently has been identified as an important strategy for Mycobacterium tuberculosis (Mtb) to evade host immune responses. However, it is unknown what role microRNA-144-3p (miR-144-3p) plays in cellular metabolism during Mtb infection. Here, we report the meaning of miR-144-3p-mediated lipid accumulation for Mtb-macrophage interplay. Mtb infection was shown to upregulate the expression of miR-144-3p in macrophages. By targeting peroxisome proliferator-activated receptor α (PPARα) and ATP-binding cassette transporter A1 (ABCA1), miR-144-3p overexpression promoted lipid accumulation and bacterial survival in Mtb-infected macrophages, while miR-144-3p inhibition had the opposite effect. Furthermore, reprogramming of host lipid metabolism by miR-144-3p suppressed autophagy in response to Mtb infection. Our findings uncover that miR-144-3p regulates host metabolism and immune responses to Mtb by targeting PPARα and ABCA1, suggesting a potential host-directed tuberculosis therapy by targeting the interface of miRNA and lipid metabolism.

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Section: Discussionsupporting

confidence: 87%

MicroRNA-144-3p Inhibits Host Lipid Catabolism and Autophagy by Targeting PPARα and ABCA1 During Mycobacterium Tuberculosis Infection

Wu,

Zhang,

Tang

et al. 2024

ACS Infect. Dis.

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“…Pro‐inflammatory neutrophils (Neu1) had downregulated KLF2 . Reduced KLF2 levels can promote neutrophil migration [26] and exacerbate NET‐induced transfusion‐related acute lung injury [27]. In the ISG high neutrophils (Neu2), we observed upregulation of ADGRE5 , also known as CD97 , which may promote migration of ISG high neutrophils to the lungs [28].…”

Section: Resultsmentioning

confidence: 99%

Single‐cell profiling of bronchoalveolar cells reveals a Th17 signature in neutrophilic severe equine asthma

Sage,

Leeb,

Jagannathan

et al. 2023

Immunology

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Severe equine asthma (SEA) is a complex respiratory condition characterized by chronic airway inflammation. It shares many clinical and pathological features with human neutrophilic asthma, making it a valuable model for studying this condition. However, the immune mechanisms driving SEA have remained elusive. Although SEA has been primarily associated with a Th2 response, there have also been reports of Th1, Th17, or mixed‐mediated responses. To uncover the elusive immune mechanisms driving SEA, we performed single‐cell mRNA sequencing (scRNA‐seq) on cryopreserved bronchoalveolar cells from 11 Warmblood horses, 5 controls and 6 with SEA. We identified six major cell types, including B cells, T cells, monocytes–macrophages, dendritic cells, neutrophils, and mast cells. All cell types exhibited significant heterogeneity, with previously identified and novel cell subtypes. Notably, we observed monocyte–lymphocyte complexes and detected a robust Th17 signature in SEA, with CXCL13 upregulation in intermediate monocytes. Asthmatic horses exhibited expansion of the B‐cell population, Th17 polarization of the T‐cell populations, and dysregulation of genes associated with T‐cell function. Neutrophils demonstrated enhanced migratory capacity and heightened aptitude for neutrophil extracellular trap formation. These findings provide compelling evidence for a predominant Th17 immune response in neutrophilic SEA, driven by dysregulation of monocyte and T‐cell genes. The dysregulated genes identified through scRNA‐seq have potential as biomarkers and therapeutic targets for SEA and provide insights into human neutrophilic asthma.

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“…TRALI mainly occurs due to the presence of HLA or HNA antibodies in the transfused blood, and in some cases, due to lipids or aging blood cells in the transfused blood (17,18). The "two-hit" theory of TRALI, suggests that the rst hitis triggered by lipopolysaccharide (LPS) endotoxin, which activates receptor endothelial cells and leads to increased expression of intercellular adhesion molecule-1 (ICAM-1) and the release of chemokines that recruit and activate neutrophils (19). The second hit occurs when HLA or HNA antibodies bind to the cognate antigens expressed on the neutrophils, activating a cascade of neutrophil reactions that release reactive oxygen species, leading to damage to surrounding the lung tissue, lung leakage, and the development of TRALI symptoms.…”

Section: Discussionmentioning

confidence: 99%

Attenuation of transfusion-related acute lung injury by FAK inhibitor PF-562271

Bai,

He,

Gang

et al. 2023

Preprint

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Background Transfusion-related acute lung injury (TRALI) is a specific form of acute lung injury (ALI) that can cause complications such as respiratory distress, hypoxia, fever, and tachycardia in patients. In some cases, symptoms can develop within 6 h of a transfusion, and chest X-rays may reveal bilateral lung opacity. A study using mice found that the focal adhesion kinase (FAK) inhibitor PF-562271 improved ALI. Methods For the study, male BALB/Cmice aged 6–8 weeks were randomly assigned to four groups: a blank control group, a group injected with lipopolysaccharide (LPS), a group injected with LPS and 5-day stored platelets (TRALI mouse model), and a group treated with the FAK inhibitor. Pathological changes in the lung tissue, lung wet/dry weight ratio, myeloperoxidase (MPO) activity, and the expression of TNF-α, IL-6, IL-8, and FAK protein were analyzed to determine the effects of the FAK inhibitor on TRALI in mice. Results Histological analysis revealed that the alveolar interstitium was filled with inflammatory cells and the alveolar septum was significantly widened in the model group. The lung wet/dry weight ratio confirmed that the pulmonary edema induced by the model group was more severe than that of the LPS group. MPO activity was higher in the TRALI group than in the LPS group. The mRNA expression of TNF-α, IL-6, IL-8, and the protein expression of FAK in the lung tissue were up-regulated. After 24 h of FAK inhibitor intervention, the pulmonary edema in TRALI mice was significantly reduced, the infiltration of inflammatory cells in lung tissue was improved, the lung function was better, and the expression of inflammatory factors was downregulated. Conclusions The study successfully constructed a mouse TRALI model infused with aged platelets and found that the FAK inhibitor can alleviate the lung injury caused by TRALI and increase the survival rate of TRALI. Therefore, FAK inhibitors may have potential applications in the treatment of TRALI.

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MiR‐144‐induced KLF2 inhibition and NF‐kappaB/CXCR1 activation promote neutrophil extracellular trap–induced transfusion‐related acute lung injury

Abstract: This is an open access article under the terms of the Creat ive Commo ns Attri bution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Cited by 15 publications

References 44 publications

MicroRNA-144-3p Inhibits Host Lipid Catabolism and Autophagy by Targeting PPARα and ABCA1 During Mycobacterium Tuberculosis Infection

MicroRNA-144-3p Inhibits Host Lipid Catabolism and Autophagy by Targeting PPARα and ABCA1 During Mycobacterium Tuberculosis Infection

Single‐cell profiling of bronchoalveolar cells reveals a Th17 signature in neutrophilic severe equine asthma

Attenuation of transfusion-related acute lung injury by FAK inhibitor PF-562271

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