Polarization of M2 macrophages requires Lamtor1 that integrates cytokine and amino-acid signals

被引：150

作者：

Kimura, Tetsuya ^{[1
,2
,3
]}

Nada, Shigeyuki ^{[4
]}

Takegahara, Noriko ^{[1
]}

Okuno, Tatsusada ^{[1
,5
]}

Nojima, Satoshi ^{[1
,3
,6
]}

Kang, Sujin ^{[1
,2
,3
]}

Ito, Daisuke ^{[1
,2
,3
]}

Morimoto, Keiko ^{[1
,2
,3
]}

Hosokawa, Takashi ^{[1
,2
,3
]}

Hayama, Yoshitomo ^{[1
,2
,3
]}

Mitsui, Yuichi ^{[1
,2
]}

Sakurai, Natsuki ^{[1
]}

Sarashina-Kida, Hana ^{[1
,2
,3
]}

Nishide, Masayuki ^{[1
,2
,3
]}

Maeda, Yohei ^{[1
,2
,3
]}

Takamatsu, Hyota ^{[1
,2
,3
]}

Okuzaki, Daisuke ^{[7
]}

Yamada, Masaki ^{[8
]}

Okada, Masato

Kumanogoh, Atsushi ^{[1
,2
,3
]}

机构：

[1] Osaka Univ, World Premier Int Immunol Frontier Res Ctr, Dept Immunopathol, Yamadaoka 2-2, Osaka 5650871, Japan

[2] Osaka Univ, Grad Sch Med, Dept Resp Med Allergy & Rheumat Dis, Yamadaoka 2-2, Osaka 5650871, Japan

[3] Japan Agcy Med Res & Dev AMED CREST, Gobancho 7, Tokyo 1020076, Japan

[4] Osaka Univ, Microbial Dis Res Inst, Dept Oncogene Res, Yamadaoka 3-1, Osaka 5650871, Japan

[5] Osaka Univ, Grad Sch Med, Dept Neurol, Yamadaoka 2-2, Osaka 5650871, Japan

[6] Osaka Univ, Grad Sch Med, Dept Pathol, Yamadaoka 2-2, Osaka 5650871, Japan

[7] DNA Chip Dev Ctr Infect Dis, Microbial Dis Res Inst, Yamadaoka 3-1, Osaka 5650871, Japan

[8] Shimadzu Co Ltd, Analyt & Measuring Instruments Div, Global Applicat Dev Ctr, Kyoto 6048511, Japan

来源：

NATURE COMMUNICATIONS | 2016年 / 7卷

基金：

日本学术振兴会;

关键词：

LXR-ALPHA; ALTERNATIVE ACTIVATION; APOPTOTIC CELLS; RAG GTPASES; IN-VIVO; MTORC1; PATHWAY; INFLAMMATION; PROLIFERATION; METABOLISM;

D O I：

10.1038/ncomms13130

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

Macrophages play crucial roles in host defence and tissue homoeostasis, processes in which both environmental stimuli and intracellularly generated metabolites influence activation of macrophages. Activated macrophages are classified into M1 and M2 macrophages. It remains unclear how intracellular nutrition sufficiency, especially for amino acid, influences on macrophage activation. Here we show that a lysosomal adaptor protein Lamtor1, which forms an amino-acid sensing complex with lysosomal vacuolar-type H+-ATPase (v-ATPase), and is the scaffold for amino acid-activated mTORC1 (mechanistic target of rapamycin complex 1), is critically required for M2 polarization. Lamtor1 deficiency, amino-acid starvation, or inhibition of v-ATPase and mTOR result in defective M2 polarization and enhanced M1 polarization. Furthermore, we identified liver X receptor (LXR) as the downstream target of Lamtor1 and mTORC1. Production of 25-hydroxycholesterol is dependent on Lamtor1 and mTORC1. Our findings demonstrate that Lamtor1 plays an essential role in M2 polarization, coupling immunity and metabolism.

引用

页数：15

共 43 条

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