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

Abstract：

: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.

journal_name

Nat Commun

journal_title

Nature communications

authors

Kimura T,Nada S,Takegahara N,Okuno T,Nojima S,Kang S,Ito D,Morimoto K,Hosokawa T,Hayama Y,Mitsui Y,Sakurai N,Sarashina-Kida H,Nishide M,Maeda Y,Takamatsu H,Okuzaki D,Yamada M,Okada M,Kumanogoh A

doi

10.1038/ncomms13130

subject

Has Abstract

pub_date

2016-10-12 00:00:00

pages

13130

issn

2041-1723

pii

ncomms13130

journal_volume

7

pub_type

杂志文章

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