ArticleThe Journal of clinical investigation2022
ALK1 signaling is required for the homeostasis of Kupffer cells and prevention of bacterial infection.
Article in The Journal of clinical investigation, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 61 citations in OpenAlex.
- Multi-level transcriptional control of specific macrophage responses.The EMBO journal · 2026Review
- Kupffer cells in liver homeostasis and disease: from immune sentinels to metabolic gatekeepers.Nature reviews. Immunology · 2026Review
- Kupffer cells: Orchestrators of liver physiology.Liver research (Beijing, China) · 2026Review
- The Key Role of Complement Receptor CRIg in Kupffer Cell-Mediated Liver Disease Progression.Viruses · 2026Review
- CHB-Induced Immune Zonation Chaos Elicited LXRα-mediated Lipid Metabolism Disorders in Kupffer Cells to Induce Cancer Stem Cell Formation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- The Role of Kupffer Cells and Liver Macrophages in the Pathogenesis of Metabolic Dysfunction-Associated Steatotic Liver Disease.Biomedicines · 2026Review
- Microbial exposure and host responses to infection reshape the disease trajectory of MASLD.Frontiers in cellular and infection microbiology · 2026Review
- Bone morphogenetic protein (BMP)-9, a systemic homeostasis factor with diverse functions in the liver and beyond.Bioscience reports · 2025Review
- Extracellular matrices regulate extravasation journey of leukocytes and inflammatory tissue fate.eLife · 2025Review
- Liver as a key organ for systemic antimicrobial defense.Hepatology communications · 2025Review
- Myeloid cells in chronic liver inflammation.Cellular & molecular immunology · 2025Review
- Hepcidin sustains Kupffer cell immune defense against bloodstream bacterial infection via gut-derived metabolites in mice.The Journal of clinical investigation · 2025Article
- Hepatic stellate cells: balancing homeostasis, hepatoprotection and fibrogenesis in health and disease.Nature reviews. Gastroenterology & hepatology · 2025Review
- A historical perspective of Kupffer cells in the context of infection.Cell and tissue research · 2025Review
- Kupffer cell and recruited macrophage heterogeneity orchestrate granuloma maturation and hepatic immunity in visceral leishmaniasis.Nature communications · 2025Article
- How oxygenation shapes immune responses: emerging roles for physioxia and pathological hypoxia.Nature reviews. Immunology · 2025Review
- Polydopamine grafting polyether ether ketone to stabilize growth factor for efficient osteonecrosis repair.Scientific reports · 2025Article
- Macrophage-tregs crosstalk: the "hub" of the immune network in MASLD.Frontiers in immunology · 2025Review
- Understanding the complex macrophage landscape in MASLD.JHEP reports : innovation in hepatology · 2024Review
- BMP10 Knockdown Modulates Endothelial Cell Immunoreactivity by Inhibiting the HIF-1α Pathway in the Sepsis-Induced Myocardial Injury.Journal of cellular and molecular medicine · 2024Article
Corrections and comments
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Authors and funding
13 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Macrophages are highly heterogeneous immune cells that fulfill tissue-specific functions. Tissue-derived signals play a critical role in determining macrophage heterogeneity. However, these signals remain largely unknown. The BMP receptor activin receptor-like kinase 1 (ALK1) is well known for its role in blood vessel formation; however, its role within the immune system has never been revealed to our knowledge. Here, we found that BMP9/BMP10/ALK1 signaling controlled the identity and self-renewal of Kupffer cells (KCs) through a Smad4-dependent pathway. In contrast, ALK1 was dispensable for the maintenance of macrophages located in the lung, kidney, spleen, and brain. Following ALK1 deletion, KCs were lost over time and were replaced by monocyte-derived macrophages. These hepatic macrophages showed significantly reduced expression of the complement receptor VSIG4 and alterations in immune zonation and morphology, which is important for the tissue-specialized function of KCs. Furthermore, we found that this signaling pathway was important for KC-mediated Listeria monocytogenes capture, as the loss of ALK1 and Smad4 led to a failure of bacterial capture and overwhelming disseminated infections. Thus, ALK1 signaling instructs a tissue-specific phenotype that allows KCs to protect the host from systemic bacterial dissemination.
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