Publication Database

SEPTIN2 suppresses an IFN-γ-independent, proinflammatory macrophage activation pathway (2023)

Art

Zeitschriftenartikel / wissenschaftlicher Beitrag

Autoren

Fu, Beibei

Xiong, Yan

Sha, Zhou

Xue, Weiwei

Xu, Binbin

Tan, Shun

Guo, Dong

Lin, Feng

Wang, Lulu

Ji, Jianjian

Luo, Yang

Lin, Xiaoyuan (WE 5)

Wu, Haibo

Quelle

Nature Communications

Bandzählung: 14

Heftzählung: 1

Seiten: Artikel 7441

ISSN: 2041-1723

Sprache

Englisch

Verweise

URL (Volltext): https://www.nature.com/articles/s41467-023-43283-2

DOI: 10.1038/s41467-023-43283-2

Pubmed: 37978190

Kontakt

Institut für Virologie

Robert-von-Ostertag-Str. 7-13
14163 Berlin
+49 30 838 51833
virologie@vetmed.fu-berlin.de

Abstract / Zusammenfassung

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.