SOCS3 Attenuates GM-CSF/IFN-γ-Mediated Inflammation During Spontaneous Spinal Cord Regeneration

SOCS3, a feedback inhibitor of the JAK/STAT signal pathway, negatively regulates axonal regrowth and inflammation in the central nervous system (CNS). Here, we demonstrated a distinct role of SOCS3 in the injured spinal cord of the gecko following tail amputation. Severing the gecko spinal cord did not evoke an inflammatory cascade except for an injury-stimulated elevation of the granulocyte/macrophage colony-stimulating factor (GM-CSF) and interferon gamma (IFN-γ) cytokines. Simultaneously, the expression of SOCS3 was upregulated in microglia, and unexpectedly not in neurons. Enforced expression of SOCS3 was sufficient to suppress the GM-CSF/IFN-γ-driven inflammatory responses through its KIR domain by attenuating the activities of JAK1 and JAK2. SOCS3 was also linked to GM-CSF/IFN-γ-induced cross-tolerance. Transfection of adenovirus overexpressing SOCS3 in the injured cord resulted in a significant decrease of inflammatory cytokines. These results reveal a distinct role of SOCS3 in the regenerating spinal cord, and provide new hints for CNS repair in mammals.

Medienart:

E-Artikel

Erscheinungsjahr:

2020

Erschienen:

2020

Enthalten in:

Zur Gesamtaufnahme - volume:36

Enthalten in:

Neuroscience bulletin - 36(2020), 7 vom: 18. Juli, Seite 778-792

Sprache:

Englisch

Beteiligte Personen:

Zhang, Xuejie [VerfasserIn]
He, Bingqiang [VerfasserIn]
Li, Hui [VerfasserIn]
Wang, Yingjie [VerfasserIn]
Zhou, Yue [VerfasserIn]
Wang, Wenjuan [VerfasserIn]
Song, Tiancheng [VerfasserIn]
Du, Nan [VerfasserIn]
Gu, Xingxing [VerfasserIn]
Luo, Yi [VerfasserIn]
Wang, Yongjun [VerfasserIn]

Links:

Volltext

Themen:

82115-62-6
83869-56-1
Cytokine
Granulocyte-Macrophage Colony-Stimulating Factor
Inflammation
Interferon-gamma
Journal Article
SOCS3
Spinal cord
Suppressor of Cytokine Signaling 3 Protein
Vertebrate

Anmerkungen:

Date Completed 19.07.2021

Date Revised 19.07.2021

published: Print-Electronic

Citation Status MEDLINE

doi:

10.1007/s12264-020-00493-8

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM308910001