ArticleFrontiers in immunology2019
Metabolic Reprograming of Cystic Fibrosis Macrophages via the IRE1α Arm of the Unfolded Protein Response Results in Exacerbated Inflammation.
Article in Frontiers in immunology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 54 citations in OpenAlex.
- The CXCR2-XBP1-NF-κB Axis Drives Inflammatory Amplification and Tissue Damage in Acute Lung Injury.Inflammation · 2026Article
- The importance of mitochondria and mitochondrial calcium signaling in health and disease: an updated outlook on inflammation.Journal of translational medicine · 2026Review
- The Involvement of MicroRNAs in Innate Immunity and Cystic Fibrosis Lung Disease: A Narrative Review.Current issues in molecular biology · 2026Review
- Pneumonia and parapneumonic pleural effusions in adults with cystic fibrosis.ERJ open research · 2025Article
- Innate Immunity in Cystic Fibrosis: Varied Effects of CFTR Modulator Therapy on Cell-to-Cell Communication.International journal of molecular sciences · 2025Review
- Article
- IRE1α pathway: A potential bone metabolism mediator.Cell proliferation · 2024Review
- CFTR is required for zinc-mediated antibacterial defense in human macrophages.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Anti-inflammatory effects of elexacaftor/tezacaftor/ivacaftor in adults with cystic fibrosis heterozygous for F508del.PloS one · 2024Article
- Review
- Hypertonic saline induces inflammation in human macrophages through the NLRP1 inflammasome.Genes and immunity · 2023Article
- Why Is Iron Deficiency/Anemia Linked to Alzheimer's Disease and Its Comorbidities, and How Is It Prevented?Biomedicines · 2023Review
- Comparative effects of CFTR modulators on phagocytic, metabolic and inflammatory profiles of CF and nonCF macrophages.Scientific reports · 2023Article
- Macrophage Reprogramming via the Modulation of Unfolded Protein Response with siRNA-Loaded Magnetic Nanoparticles in a TAM-like Experimental Model.Pharmaceutics · 2023Article
- Dynamic atlas of immune cells reveals multiple functional features of macrophages associated with progression of pulmonary fibrosis.Frontiers in immunology · 2023Article
- Loss of CFTR function in macrophages alters the cell transcriptional program and delays lung resolution of inflammation.Frontiers in immunology · 2023Article
- Novel XBP1s-independent function of IRE1 RNase in HIF-1α-mediated glycolysis upregulation in human macrophages upon stimulation with LPS or saturated fatty acid.Frontiers in immunology · 2023Article
- The Impact of Highly Effective Modulator Therapy on Cystic Fibrosis Microbiology and Inflammation.Clinics in chest medicine · 2022Review
- MicroRNA global profiling in cystic fibrosis cell lines reveals dysregulated pathways related with inflammation, cancer, growth, glucose and lipid metabolism, and fertility: an exploratory study.Acta bio-medica : Atenei Parmensis · 2022Article
- A Non-Canonical Role for IRE1α Links ER and Mitochondria as Key Regulators of Astrocyte Dysfunction: Implications in Methamphetamine use and HIV-Associated Neurocognitive Disorders.Frontiers in neuroscience · 2022Article
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cystic Fibrosis (CF) is a recessive genetic disorder caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR). CFTR mutations cause dysregulation of channel function with intracellular accumulation of misfolded proteins and endoplasmic reticulum (ER) stress, with activation of the IRE1α-XBP1 pathway that regulates a subset of unfolded protein response (UPR) genes. This pathway regulates a group of genes that control proinflammatory and metabolic responses in different immune cells; however, the metabolic state of immune cells and the role of this pathway in CF remain elusive. Our results indicate that only innate immune cells from CF patients present increased levels of ER stress, mainly affecting neutrophils, monocytes, and macrophages. An overactive IRE1α-XBP1 pathway reprograms CF M1 macrophages toward an increased metabolic state, with increased glycolytic rates and mitochondrial function, associated with exaggerated production of TNF and IL-6. This hyper-metabolic state, seen in CF macrophages, is reversed by inhibiting the RNase domain of IRE1α, thereby decreasing the increased glycolic rates, mitochondrial function and inflammation. Altogether, our results indicate that innate immune cells from CF patients are primarily affected by ER stress. Moreover, the IRE1α-XBP1 pathway of the UPR is responsible for the hyper-metabolic state seen in CF macrophages, which is associated with the exaggerated inflammatory response. Modulating ER stress, metabolism and inflammation, by targeting IRE1α, may improve the metabolic fitness of macrophages, and other immune cells in CF and other immune-related disorders.
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