The Jmjd3-Irf4 axis regulates M2 macrophage polarization and host responses against helminth infection.
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.
Satoh
Takashi
T
Laboratory of Host Defense, World Premiere Initiative Immunology Frontier Research Center, Osaka University, Osaka, Japan.
Takeuchi
Osamu
O
Vandenbon
Alexis
A
Yasuda
Koubun
K
Tanaka
Yoshiaki
Y
Kumagai
Yutaro
Y
Miyake
Tohru
T
Matsushita
Kazufumi
K
Okazaki
Toshihiko
T
Saitoh
Tatsuya
T
Honma
Kiri
K
Matsuyama
Toshifumi
T
Yui
Katsuyuki
K
Tsujimura
Tohru
T
Standley
Daron M
DM
Nakanishi
Kenji
K
Nakai
Kenta
K
Akira
Shizuo
S
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
D002686:Chitin; D056466:Histone Demethylases; D050835:Interferon Regulatory Factors; D056484:Jumonji Domain-Containing Histone Demethylases; D000099218:Interferon Regulatory Factor-4; C523761:Kdm6b protein, mouse