ArticleJournal of immunology (Baltimore, Md. : 1950)2016
IRF4 and IRF8 Act in CD11c+ Cells To Regulate Terminal Differentiation of Lung Tissue Dendritic Cells.
Article in Journal of immunology (Baltimore, Md. : 1950), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers.
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Who cites it
64 citing papers in PubMed, 95 citations in OpenAlex.
- Tumor-induced dendritic cell deregulation perturbs T cell proliferation and predicts clinical outcome in acute lymphoblastic leukemia.Cell reports. Medicine · 2026Article
- Homeostatic Regulation of Lung Dendritic Cells at Steady State.Immune network · 2026Review
- Interferon Regulatory Factors in Alcohol-Associated Liver Disease: Cell-Type Programs, Danger Signaling, and Therapeutic Opportunities.Current issues in molecular biology · 2026Review
- Bridging pDCs and cDCs: The Identity of Transitional Dendritic Cells.Immunological reviews · 2025Review
- PU.1 and TGF-β signaling activate the cell-surface expression of CD103 in mast cells and dendritic cells: opposite roles of GATA2 in the expression of mucosal mast cell genes.The FEBS journal · 2025Article
- Functional Specialization and Collaboration of cDC2 Subsets in CD4+ T Cell Priming and Differentiation.Immunological reviews · 2025Review
- IRF4-regulated transcriptional and functional heterogeneity of lung-resident CD11b+ cDC2 subsets during influenza virus infection.Journal of immunology (Baltimore, Md. : 1950) · 2025Article
- Role of USP7 in the regulation of tolerogenic dendritic cell function in type 1 diabetes.Cellular & molecular biology letters · 2025Article
- CD11c-Cre driven deletion ofFrontiers in immunology · 2025Article
- Lung disease in relation to unique monocyte-macrophage subpopulations induced by combined inhalant endotoxin and collagen-induced arthritis.Frontiers in immunology · 2025Article
- Acquired immunostimulatory phenotype of migratory CD103+ DCs promotes alloimmunity following corneal transplantation.JCI insight · 2024Article
- The role of dendritic cells in respiratory viral infection.European respiratory review : an official journal of the European Respiratory Society · 2024Review
- EvaluatingFrontiers in immunology · 2024Review
- Effect of Apremilast on LPS-induced immunomodulation and inflammation via activation of Nrf2/HO-1 pathways in rat lungs.Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society · 2023Article
- Activation of regulatory dendritic cells by Mertk coincides with a temporal wave of apoptosis in neonatal lungs.Science immunology · 2023Article
- Catching Our Breath: Updates on the Role of Dendritic Cell Subsets in Asthma.Advanced biology · 2023Review
- Signaling pathways involved in the biological functions of dendritic cells and their implications for disease treatment.Molecular biomedicine · 2023Review
- Early-life hyperoxia-induced Flt3L drives neonatal lung dendritic cell expansion and proinflammatory responses.Frontiers in immunology · 2023Article
- The innate immune brakes of the lung.Frontiers in immunology · 2023Review
- IRF4 expression by lung dendritic cells drives acute but not Trm cell-dependent memory Th2 responses.JCI insight · 2022Article
4 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Dendritic cells (DCs) initiate immune responses in barrier tissues including lung and skin. Conventional DC (cDC) subsets, CD11b(-) (cDC1s) or CD11b(+) (cDC2s), arise via distinct networks of transcription factors involving IFN regulatory factor 4 (IRF4) and IRF8, and are specialized for unique functional responses. Using mice in which a conditional Irf4 or Irf8 allele is deleted in CD11c(+) cells, we determined whether IRF4 or IRF8 deficiency beginning in CD11c(+) cDC precursors (pre-cDCs) changed the homeostasis of mature DCs or pre-DCs in the lung, dermis, and spleen. CD11c-cre-Irf4(-/-) mice selectively lacked a lung-resident CD11c(hi)CD11b(+)SIRPα(+)CD24(+) DC subset, but not other lung CD11b(+) DCs or alveolar macrophages. Numbers of CD11b(+)CD4(+) splenic DCs, but not CD11b(+) dermal DCs, were reduced, indicating cDC2s in the lung and dermis develop via different pathways. Irf4 deficiency did not alter numbers of cDC1s. CD11c-cre-Irf8(-/-) mice lacked lung-resident CD103(+) DCs and splenic CD8α(+) DCs, yet harbored increased IRF4-dependent DCs. This correlated with a reduced number of Irf8(-/-) pre-cDCs, which contained elevated IRF4, suggesting that Irf8 deficiency diverts pre-cDC fate. Analyses of Irf4 and Irf8 haploinsufficient mice showed that, although one Irf4 allele was sufficient for lung cDC2 development, two functional Irf8 alleles were required for differentiation of lung cDC1s. Thus, IRF8 and IRF4 act in pre-cDCs to direct the terminal differentiation of cDC1 and cDC2 subsets in the lung and spleen. These data suggest that variation in IRF4 or IRF8 levels resulting from genetic polymorphisms or environmental cues will govern tissue DC numbers and, therefore, regulate the magnitude of DC functional responses.
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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 OpenQuestion graph.