The LPS-inducible lncRNA Mirt2 is a negative regulator of inflammation

Meng Du; Lin Yuan; Xin Tan; Dandan Huang; Xiaojing Wang; Zhe Zheng; Xiaoxiang Mao; Xiangrao Li; Liu Yang; Kun Huang; Fengxiao Zhang; Yan Wang; Xi Luo; Dan Huang; Kai Huang

doi:10.1038/s41467-017-02229-1

The LPS-inducible lncRNA Mirt2 is a negative regulator of inflammation

Meng Du, Lin Yuan, Xin Tan, Dandan Huang, Xiaojing Wang, Zhe Zheng, Xiaoxiang Mao, Xiangrao Li, Liu Yang, Kun Huang, Fengxiao Zhang, Yan Wang, Xi Luo, Dan Huang, Kai Huang

Research output: Contribution to journal › Article › peer-review

197 Scopus citations

Abstract

Toll-like receptors (TLRs) are a family of pattern recognition receptors (PRR) with a crucial function in innate immune responses. Activation of TLR4 signaling at the plasma membrane by lipopolysaccharide (LPS) stimulates proinflammatory signaling pathways dependent on the E3 ubiquitin ligase TRAF6. Here we show the LPS-induced long non-coding RNA (lncRNA) Mirt2 functions as a checkpoint to prevent aberrant activation of inflammation, and is a potential regulator of macrophage polarization. Mirt2 associates with, and attenuates Lys63 (K63)-linked ubiquitination of, TRAF6, thus inhibiting activation of NF-κB and MAPK pathways and limiting production of proinflammatory cytokines. Adenovirus mediated gene transfer of Mirt2 protects mice from endotoxemia induced fatality and multi-organ dysfunction. These findings identify lncRNA Mirt2 as a negative feedback regulator of excessive inflammation.

Original language	English (US)
Article number	2049
Journal	Nature communications
Volume	8
Issue number	1
DOIs	https://doi.org/10.1038/s41467-017-02229-1
State	Published - Dec 1 2017
Externally published	Yes

ASJC Scopus subject areas

General Chemistry
General Biochemistry, Genetics and Molecular Biology
General Physics and Astronomy

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10.1038/s41467-017-02229-1

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title = "The LPS-inducible lncRNA Mirt2 is a negative regulator of inflammation",

abstract = "Toll-like receptors (TLRs) are a family of pattern recognition receptors (PRR) with a crucial function in innate immune responses. Activation of TLR4 signaling at the plasma membrane by lipopolysaccharide (LPS) stimulates proinflammatory signaling pathways dependent on the E3 ubiquitin ligase TRAF6. Here we show the LPS-induced long non-coding RNA (lncRNA) Mirt2 functions as a checkpoint to prevent aberrant activation of inflammation, and is a potential regulator of macrophage polarization. Mirt2 associates with, and attenuates Lys63 (K63)-linked ubiquitination of, TRAF6, thus inhibiting activation of NF-κB and MAPK pathways and limiting production of proinflammatory cytokines. Adenovirus mediated gene transfer of Mirt2 protects mice from endotoxemia induced fatality and multi-organ dysfunction. These findings identify lncRNA Mirt2 as a negative feedback regulator of excessive inflammation.",

author = "Meng Du and Lin Yuan and Xin Tan and Dandan Huang and Xiaojing Wang and Zhe Zheng and Xiaoxiang Mao and Xiangrao Li and Liu Yang and Kun Huang and Fengxiao Zhang and Yan Wang and Xi Luo and Dan Huang and Kai Huang",

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AU - Du, Meng

AU - Yuan, Lin

AU - Tan, Xin

AU - Huang, Dandan

AU - Wang, Xiaojing

AU - Zheng, Zhe

AU - Mao, Xiaoxiang

AU - Li, Xiangrao

AU - Yang, Liu

AU - Huang, Kun

AU - Zhang, Fengxiao

AU - Wang, Yan

AU - Luo, Xi

AU - Huang, Dan

AU - Huang, Kai

PY - 2017/12/1

Y1 - 2017/12/1

N2 - Toll-like receptors (TLRs) are a family of pattern recognition receptors (PRR) with a crucial function in innate immune responses. Activation of TLR4 signaling at the plasma membrane by lipopolysaccharide (LPS) stimulates proinflammatory signaling pathways dependent on the E3 ubiquitin ligase TRAF6. Here we show the LPS-induced long non-coding RNA (lncRNA) Mirt2 functions as a checkpoint to prevent aberrant activation of inflammation, and is a potential regulator of macrophage polarization. Mirt2 associates with, and attenuates Lys63 (K63)-linked ubiquitination of, TRAF6, thus inhibiting activation of NF-κB and MAPK pathways and limiting production of proinflammatory cytokines. Adenovirus mediated gene transfer of Mirt2 protects mice from endotoxemia induced fatality and multi-organ dysfunction. These findings identify lncRNA Mirt2 as a negative feedback regulator of excessive inflammation.

AB - Toll-like receptors (TLRs) are a family of pattern recognition receptors (PRR) with a crucial function in innate immune responses. Activation of TLR4 signaling at the plasma membrane by lipopolysaccharide (LPS) stimulates proinflammatory signaling pathways dependent on the E3 ubiquitin ligase TRAF6. Here we show the LPS-induced long non-coding RNA (lncRNA) Mirt2 functions as a checkpoint to prevent aberrant activation of inflammation, and is a potential regulator of macrophage polarization. Mirt2 associates with, and attenuates Lys63 (K63)-linked ubiquitination of, TRAF6, thus inhibiting activation of NF-κB and MAPK pathways and limiting production of proinflammatory cytokines. Adenovirus mediated gene transfer of Mirt2 protects mice from endotoxemia induced fatality and multi-organ dysfunction. These findings identify lncRNA Mirt2 as a negative feedback regulator of excessive inflammation.

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The LPS-inducible lncRNA Mirt2 is a negative regulator of inflammation

Abstract

ASJC Scopus subject areas

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