dc.contributor.author
Fu, Beibei
dc.contributor.author
Xiong, Yan
dc.contributor.author
Sha, Zhou
dc.contributor.author
Xue, Weiwei
dc.contributor.author
Xu, Binbin
dc.contributor.author
Tan, Shun
dc.contributor.author
Guo, Dong
dc.contributor.author
Lin, Feng
dc.contributor.author
Wang, Lulu
dc.contributor.author
Lin, Xiaoyuan
dc.date.accessioned
2024-02-07T07:43:58Z
dc.date.available
2024-02-07T07:43:58Z
dc.identifier.uri
https://refubium.fu-berlin.de/handle/fub188/42340
dc.identifier.uri
http://dx.doi.org/10.17169/refubium-42065
dc.description.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.
en
dc.format.extent
19 Seiten
dc.rights.uri
https://creativecommons.org/licenses/by/4.0/
dc.subject
Inflammation
en
dc.subject
Monocytes and macrophages
en
dc.subject.ddc
500 Naturwissenschaften und Mathematik::570 Biowissenschaften; Biologie::570 Biowissenschaften; Biologie
dc.title
SEPTIN2 suppresses an IFN-γ-independent, proinflammatory macrophage activation pathway
dc.type
Wissenschaftlicher Artikel
dcterms.bibliographicCitation.articlenumber
7441
dcterms.bibliographicCitation.doi
10.1038/s41467-023-43283-2
dcterms.bibliographicCitation.journaltitle
Nature Communications
dcterms.bibliographicCitation.volume
14
dcterms.bibliographicCitation.url
https://doi.org/10.1038/s41467-023-43283-2
refubium.affiliation
Veterinärmedizin
refubium.affiliation.other
Institut für Virologie

refubium.resourceType.isindependentpub
no
dcterms.accessRights.openaire
open access
dcterms.isPartOf.eissn
2041-1723
refubium.resourceType.provider
WoS-Alert