title: 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.
authors: Laboratory of Host Defense, World Premiere Initiative Immunology Frontier Research Center, Osaka University, Osaka, Japan.
authors: Takashi
authors: T
authors: Satoh
authors: Osamu
authors: O
authors: Takeuchi
authors: Alexis
authors: A
authors: Vandenbon
authors: Koubun
authors: K
authors: Yasuda
authors: Yoshiaki
authors: Y
authors: Tanaka
authors: Yutaro
authors: Y
authors: Kumagai
authors: Tohru
authors: T
authors: Miyake
authors: Kazufumi
authors: K
authors: Matsushita
authors: Toshihiko
authors: T
authors: Okazaki
authors: Tatsuya
authors: T
authors: Saitoh
authors: Kiri
authors: K
authors: Honma
authors: Toshifumi
authors: T
authors: Matsuyama
authors: Katsuyuki
authors: K
authors: Yui
authors: Tohru
authors: T
authors: Tsujimura
authors: Daron M
authors: DM
authors: Standley
authors: Kenji
authors: K
authors: Nakanishi
authors: Kenta
authors: K
authors: Nakai
authors: Shizuo
authors: S
authors: Akira
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D016764:Cell Polarity; D002686:Chitin / Q000276:immunology; D015971:Gene Expression Regulation, Enzymologic; D056466:Histone Demethylases / Q000378:metabolism; D006790:Host-Parasite Interactions / Q000276:immunology; D050835:Interferon Regulatory Factors / Q000235:genetics / Q000276:immunology*; D056484:Jumonji Domain-Containing Histone Demethylases / Q000235:genetics / Q000276:immunology*; D008262:Macrophage Activation / Q000276:immunology*; D008264:Macrophages / Q000166:cytology / Q000276:immunology*; D016676:Macrophages, Alveolar / Q000276:immunology*; D008745:Methylation; D051379:Mice; D018345:Mice, Knockout; D009559:Nippostrongylus / Q000276:immunology*; D017206:Strongylida Infections / Q000276:immunology*; D000099218:Interferon Regulatory Factor-4
chemical_list: D002686:Chitin; D056466:Histone Demethylases; D050835:Interferon Regulatory Factors; D056484:Jumonji Domain-Containing Histone Demethylases; D000099218:Interferon Regulatory Factor-4; C523761:Kdm6b protein, mouse