Cover Image

Nuclear localization of suppressor of cytokine signaling-1 regulates local immunity in the lung

Suppressor of cytokine signaling 1 (SOCS1) is a negative feedback inhibitor of cytoplasmic Janus kinase and signal transducer and activator of transcription (STAT) signaling. SOCS1 also contains a nuclear localization sequence (NLS), yet, the in vivo importance of nuclear translocation is unknown. W...

Full description

Saved in:
Bibliographic Details
Main Authors: Zimmer, Jana (Author) , Weitnauer, Michael (Author) , Boutin, Sébastien (Author) , Küblbeck, Günter (Author) , Thiele, Sabrina (Author) , Walker, Patrick (Author) , Lasitschka, Felix (Author) , Lunding, Lars (Author) , Orinska, Zane (Author) , Vock, Christina (Author) , Arnold, Bernd (Author) , Wegmann, Michael (Author) , Dalpke, Alexander (Author)
Format: Article (Journal)
Language:English
Published: 18 November 2016
In: Frontiers in immunology
Year: 2016, Volume: 7, Pages: 1-17
ISSN:1664-3224
DOI:10.3389/fimmu.2016.00514
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.3389/fimmu.2016.00514
Verlag, lizenzpflichtig, Volltext: https://www.frontiersin.org/article/10.3389/fimmu.2016.00514
Get full text
Author Notes:Jana Zimmer, Michael Weitnauer, Sébastien Boutin, Günter Küblbeck, Sabrina Thiele, Patrick Walker, Felix Lasitschka, Lars Lunding, Zane Orinska, Christina Vock, Bernd Arnold, Michael Wegmann and Alexander Dalpke
Description
Summary:Suppressor of cytokine signaling 1 (SOCS1) is a negative feedback inhibitor of cytoplasmic Janus kinase and signal transducer and activator of transcription (STAT) signaling. SOCS1 also contains a nuclear localization sequence (NLS), yet, the in vivo importance of nuclear translocation is unknown. We generated transgenic mice containing mutated Socs1ΔNLS that fails to translocate in the cell nucleus (MGLtg mice). Whereas mice fully deficient for SOCS1 die within the first 3 weeks due to excessive interferon signaling and multiorgan inflammation, mice expressing only non-nuclear Socs1ΔNLS (Socs1−/−MGLtg mice) were rescued from early lethality. Canonical interferon gamma signaling was still functional in Socs1−/−MGLtg mice as shown by unaltered tyrosine phosphorylation of STAT1 and whole genome expression analysis. However, a subset of NFκB inducible genes was dysregulated. Socs1−/−MGLtg mice spontaneously developed low-grade inflammation in the lung and had elevated Th2-type cytokines. Upon ovalbumin sensitization and challenge, airway eosinophilia was increased in Socs1−/−MGLtg mice. Decreased transepithelial electrical resistance in trachea epithelial cells from Socs1−/−MGLtg mice suggests disrupted epithelial cell barrier. The results indicate that nuclear SOCS1 is a regulator of local immunity in the lung and unravel a so far unrecognized function for SOCS1 in the cell nucleus.
Item Description:Gesehen am 08.10.2021
Physical Description:Online Resource
ISSN:1664-3224
DOI:10.3389/fimmu.2016.00514

Similar Items