ArticleJCI insight2024
Myeloid Zfhx3 deficiency protects against hypercapnia-induced suppression of host defense against influenza A virus.
Article in JCI insight, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
8 citing papers in PubMed, 9 citations in OpenAlex.
- Astroimmunology: the effects of spaceflight and its associated stressors on the immune system.Nature reviews. Immunology · 2026Review
- Hypercapnia Effects on Lung Function.Comprehensive Physiology · 2026Review
- Sensing molecular carbon dioxide: a translational focus for respiratory disease.Physiological reviews · 2025Review
- Hypercapnia Increases Influenza A Virus Infection of Bronchial Epithelial Cells by Augmenting Cellular Cholesterol via mTOR and Akt.International journal of molecular sciences · 2025Article
- Rapamycin improves satellite cells' autophagy and muscle regeneration during hypercapnia.JCI insight · 2025Article
- Contribution of the bitter taste signaling pathway to lung inflammation duringFrontiers in immunology · 2025Article
- KLF17 is an important regulatory component of the transcriptomic response of Atlantic salmon macrophages toFrontiers in immunology · 2023Article
- Hypercapnia increases ACE2 expression and pseudo-SARS-CoV-2 entry in bronchial epithelial cells by augmenting cellular cholesterol.Frontiers in immunology · 2023Article
Corrections and comments
- Update ofMyeloid2023
Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
Hypercapnia, elevation of the partial pressure of CO2 in blood and tissues, is a risk factor for mortality in patients with severe acute and chronic lung diseases. We previously showed that hypercapnia inhibits multiple macrophage and neutrophil antimicrobial functions and that elevated CO2 increases the mortality of bacterial and viral pneumonia in mice. Here, we show that normoxic hypercapnia downregulates innate immune and antiviral gene programs in alveolar macrophages (AMØs). We also show that zinc finger homeobox 3 (Zfhx3) - a mammalian ortholog of zfh2, which mediates hypercapnic immune suppression in Drosophila - is expressed in mouse and human macrophages. Deletion of Zfhx3 in the myeloid lineage blocked the suppressive effect of hypercapnia on immune gene expression in AMØs and decreased viral replication, inflammatory lung injury, and mortality in hypercapnic mice infected with influenza A virus. To our knowledge, our results establish Zfhx3 as the first known mammalian mediator of CO2 effects on immune gene expression and lay the basis for future studies to identify therapeutic targets to interrupt hypercapnic immunosuppression in patients with advanced lung disease.
Indexed as
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What Socratic holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.