The Jmjd3-Irf4 axis regulates M2 macrophage polarization and host responses against helminth infection
Abstract
Polarization of macrophages to M1 or M2 cells is important for mounting responses against bacterial and helminth infections, respectively. Jumonji domain containing-3 (Jmjd3), a histone 3 Lys27 (H3K27) demethylase, has been implicated in the activation of macrophages. Here we show that Jmjd3 is essential for M2 macrophage polarization in response to helminth infection and chitin, though Jmjd3 is dispensable for M1 responses. Furthermore, Jmjd3 (also known as Kdm6b) is essential for proper bone marrow macrophage differentiation, and this function depends on demethylase activity of Jmjd3. Jmjd3 deficiency affected trimethylation of H3K27 in only a limited number of genes. Among them, we identified Irf4 as encoding a key transcription factor that controls M2 macrophage polarization. Collectively, these results show that Jmjd3-mediated H3K27 demethylation is crucial for regulating M2 macrophage development leading to anti-helminth host responses.
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STAT1 and IRF5 are involved in M1 polarization/maintenance; STAT6, IRF4, CREB-C/EBPβ, and PPARγ are involved in M2 polarization/maintenance.
“Specifically, STAT1 and IRF5 have been shown to be involved in polarization and maintenance of an M1 phenotype while STAT6, IRF4, CREB-C/EBPβ, and PPARγ are involved in polarization and maintenance of an M2 phenotype [23–30].”
From Macrophage polarization: an opportunity for improved outcomes in biomaterials and regenerative medicine (2012) · cites this paper as [25]
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- Authors
- Satoh, T., Takeuchi, O., Vandenbon, A., Yasuda, K., Tanaka, Y., Kumagai, Y., Miyake, T., Matsushita, K., Okazaki, T., Saitoh, T., Honma, K., Matsuyama, T., Yui, K., Tsujimura, T., Standley, D. M., Nakanishi, K., Nakai, K., & Akira, S.
- Affiliations
- Immunology Frontier Research Center, The University of Osaka (JP)
- Hyogo Medical University (JP)
- Institute of Medical Science, The University of Tokyo (JP)
- Nagasaki University (JP)
- Corresponding author
- Akira, Shizuo
- ORCID
- Venue
- Nature Immunology
- Published
- 2010-08-22
- Volume
- 11
- Issue
- 10
- Pages
- 936-944
- ISSN
- 1529-2908 (ISSN-L)
- 1529-2916
- OpenAlex
- W2133536768
- Cited by
- 1,156
- References
- 7
- Citations by year
- 2026: 33 · 2025: 44 · 2024: 54 · 2023: 74 · 2022: 81 · 2021: 99 · 2020: 77 · 2019: 58 · 2018: 89 · 2017: 99 · 2016: 74 · 2015: 82 · 2014: 94 · 2013: 74 · 2012: 64
- FWCI
- 25.44
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Immunology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Allergy and Infectious Diseases (P01AI070167)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
- Life Sciences › Immunology and Microbiology › Parasitology › Parasites and Host Interactions
- Life Sciences › Immunology and Microbiology › Immunology › Mast cells and histamine
- Keywords
- JMJD3, KDM6B, IRF4, M2 macrophage polarization, M1 macrophages, helminthiasis, H3K27 demethylation, histone demethylase, chitin, transcriptional regulation
- MeSH terms
- Interferon Regulatory Factor-4, Animals, Cell Differentiation, Chitin, Host-Parasite Interactions, Macrophage Activation, Macrophages, Methylation, Nippostrongylus, Gene Expression Regulation, Enzymologic, Macrophages, Alveolar, Cell Polarity, Strongylida Infections, Mice, Knockout, Interferon Regulatory Factors, Mice, Histone Demethylases, Jumonji Domain-Containing Histone Demethylases
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