SEPTIN2 suppresses an IFN-γ-independent, proinflammatory macrophage activation pathway

Beibei Fu, Yan Xiong, Zhou Sha, Weiwei Xue, Binbin Xu, Shun Tan, Dong Guo, Feng Lin, Lulu Wang, Jianjian Ji, Yang Luo (), Xiaoyuan Lin () and Haibo Wu ()
Additional contact information
Beibei Fu: Chongqing University
Yan Xiong: Chongqing University
Zhou Sha: Chongqing University
Weiwei Xue: Chongqing University
Binbin Xu: Chongqing University
Shun Tan: Chongqing Public Health Medical Center
Dong Guo: Chongqing University
Feng Lin: Chongqing University
Lulu Wang: Chongqing University
Jianjian Ji: Nanjing University of Chinese Medicine
Yang Luo: Chongqing University
Xiaoyuan Lin: Freie Universität Berlin
Haibo Wu: Chongqing University

Nature Communications, 2023, vol. 14, issue 1, 1-19

Abstract: Abstract Interferon-gamma (IFN-γ) signaling is necessary for the proinflammatory activation of macrophages but IFN-γ-independent pathways, for which the initiating stimuli and downstream mechanisms are lesser known, also contribute. Here we identify, by high-content screening, SEPTIN2 (SEPT2) as a negative regulation of IFN-γ-independent macrophage autoactivation. Mechanistically, endoplasmic reticulum (ER) stress induces the expression of SEPT2, which balances the competition between acetylation and ubiquitination of heat shock protein 5 at position Lysine 327, thereby alleviating ER stress and constraining M1-like polarization and proinflammatory cytokine release. Disruption of this negative feedback regulation leads to the accumulation of unfolded proteins, resulting in accelerated M1-like polarization, excessive inflammation and tissue damage. Our study thus uncovers an IFN-γ-independent macrophage proinflammatory autoactivation pathway and suggests that SEPT2 may play a role in the prevention or resolution of inflammation during infection.

Date: 2023
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-023-43283-2 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-43283-2

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-023-43283-2

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().