Autor: |
Beibei Fu, Yan Xiong, Zhou Sha, Weiwei Xue, Binbin Xu, Shun Tan, Dong Guo, Feng Lin, Lulu Wang, Jianjian Ji, Yang Luo, Xiaoyuan Lin, Haibo Wu |
Jazyk: |
angličtina |
Rok vydání: |
2023 |
Předmět: |
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Zdroj: |
Nature Communications, Vol 14, Iss 1, Pp 1-19 (2023) |
Druh dokumentu: |
article |
ISSN: |
2041-1723 |
DOI: |
10.1038/s41467-023-43283-2 |
Popis: |
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. |
Databáze: |
Directory of Open Access Journals |
Externí odkaz: |
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