The Jmjd3-Irf4 axis regulates M2 macrophage polarization and host responses against helminth infection

被引：940

作者：

Satoh, Takashi ^{[1
,2
]}

Takeuchi, Osamu ^{[1
,2
]}

Vandenbon, Alexis ^{[3
]}

Yasuda, Koubun ^{[4
]}

Tanaka, Yoshiaki ^{[5
]}

Kumagai, Yutaro ^{[1
,2
]}

Miyake, Tohru ^{[1
,2
]}

Matsushita, Kazufumi ^{[1
,2
]}

Okazaki, Toshihiko ^{[1
]}

Saitoh, Tatsuya ^{[1
,2
]}

Honma, Kiri ^{[6
]}

Matsuyama, Toshifumi ^{[6
]}

Yui, Katsuyuki ^{[6
]}

Tsujimura, Tohru ^{[7
]}

Standley, Daron M. ^{[3
]}

Nakanishi, Kenji ^{[4
]}

Nakai, Kenta ^{[6
]}

Akira, Shizuo ^{[1
,2
]}

机构：

[1] Osaka Univ, Lab Host Def, World Premiere Initiat Immunol Frontier Res Ctr, Osaka, Japan

[2] Osaka Univ, Res Inst Microbial Dis, Osaka, Japan

[3] Osaka Univ, World Premiere Int Immunol Frontier Res Ctr, Lab Syst Immunol, Osaka, Japan

[4] Hyogo Coll Med, Dept Immunol & Med Zool, Nishinomiya, Hyogo, Japan

[5] Univ Tokyo, Lab Funct Anal Silico, Ctr Human Genome, Inst Med Sci, Tokyo, Japan

[6] Nagasaki Univ, Grad Sch Biomed Sci, Dept Mol Microbiol & Immunol, Nagasaki 852, Japan

[7] Hyogo Coll Med, Dept Pathol, Nishinomiya, Hyogo, Japan

来源：

NATURE IMMUNOLOGY | 2010年 / 11卷 / 10期

基金：

美国国家卫生研究院;

关键词：

TRANSCRIPTION FACTOR IRF4; CD4(+) T-CELLS; KAPPA-B-ZETA; IMMUNE-RESPONSES; GENE-EXPRESSION; TH2; CYTOKINES; ACTIVATION; INFLAMMATION; DIFFERENTIATION; CONTRIBUTES;

D O I：

10.1038/ni.1920

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

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.

引用

页码：936 / U89

页数：10

共 43 条

[31] Transcriptional control of the inflammatory response [J].

Medzhitov, Ruslan ;

Horng, Tiffany .

NATURE REVIEWS IMMUNOLOGY, 2009, 9 (10) :692-703

[32] Novel effector molecules in type 2 inflammation: Lessons drawn from helminth infection and allergy [J].

Nair, Meera G. ;

Guild, Katherine J. ;

Artis, David .

JOURNAL OF IMMUNOLOGY, 2006, 177 (03) :1393-1399

[33] Chitinase and Fizz family members are a generalized feature of nematode infection with selective Upregulation of Ym1 and F10.1 by antigen-presenting cells [J].

Nair, MG ;

Gallagher, LJ ;

Taylor, MD ;

Loke, P ;

Coulson, PS ;

Wilson, RA ;

Maizels, RM ;

Allen, JE .

INFECTION AND IMMUNITY, 2005, 73 (01) :385-394

[34] Negative regulation of Toll-like-receptor signaling by IRF-4 [J].

Negishi, H ;

Ohba, Y ;

Yanai, H ;

Takaoka, A ;

Honma, K ;

Yui, K ;

Matsuyama, T ;

Taniguchi, T ;

Honda, K .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2005, 102 (44) :15989-15994

[35] Chitin induces accumulation in tissue of innate immune cells associated with allergy [J].

Reese, Tiffany A. ;

Liang, Hong-Erh ;

Tager, Andrew M. ;

Luster, Andrew D. ;

Van Rooijen, Nico ;

Voehringer, David ;

Locksley, Richard M. .

NATURE, 2007, 447 (7140) :92-U7

[36] TWEAK induces NF-κB2 p100 processing and long lasting NF-κB activation [J].

Saitoh, T ;

Nakayama, M ;

Nakano, H ;

Yagita, H ;

Yamamoto, N ;

Yamaoka, S .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (38) :36005-36012

[37] Genome regulation by polycomb and trithorax proteins [J].

Schuettengruber, Bernd ;

Chourrout, Daniel ;

Vervoort, Michel ;

Leblanc, Benjamin ;

Cavalli, Giacomo .

CELL, 2007, 128 (04) :735-745

[38] INTERLEUKIN-4 POTENTLY ENHANCES MURINE MACROPHAGE MANNOSE RECEPTOR ACTIVITY - A MARKER OF ALTERNATIVE IMMUNOLOGICAL MACROPHAGE ACTIVATION [J].

STEIN, M ;

KESHAV, S ;

HARRIS, N ;

GORDON, S .

JOURNAL OF EXPERIMENTAL MEDICINE, 1992, 176 (01) :287-292

[39] Pattern Recognition Receptors and Inflammation [J].

Takeuchi, Osamu ;

Akira, Shizuo .

CELL, 2010, 140 (06) :805-820

[40] Human IL-23-producing type 1 macrophages promote but IL-10-producing type 2, macrophages subvert, immunity to (myco)bacteria [J].

Verreck, FAW ;

de Boer, T ;

Langenberg, DML ;

Hoeve, MA ;

Kramer, M ;

Vaisberg, E ;

Kastelein, R ;

Kolk, A ;

de Waal-Malefyt, R ;

Ottenhoff, THM .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2004, 101 (13) :4560-4565

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