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The Jmjd3-Irf4 axis regulates M2 macrophage polarization and host responses against helminth infection
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The Jmjd3-Irf4 axis regulates M2 macrophage polarization and host responses against helminth infection
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Journal Article
The Jmjd3-Irf4 axis regulates M2 macrophage polarization and host responses against helminth infection
2010
Overview
Macrophages can be divided into two subsets, M1 and M2, which have crucial differences in their function. Akira and colleagues identify the histone demethylase Jmjd3 as a key factor in M2 development.
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.
Publisher
Nature Publishing Group US,Nature Publishing Group
Subject
/ Animals
/ Biomedical and Life Sciences
/ Chitin
/ Gene Expression Regulation, Enzymologic
/ Histone Demethylases - metabolism
/ Host-Parasite Interactions - immunology
/ Interferon Regulatory Factors - genetics
/ Interferon Regulatory Factors - immunology
/ Jumonji Domain-Containing Histone Demethylases - genetics
/ Jumonji Domain-Containing Histone Demethylases - immunology
/ Macrophage Activation - immunology
/ Macrophages, Alveolar - immunology
/ Mice
