SOCS-1/SSI-1-deficient NKT cells participate in severe hepatitis through dysregulated cross-talk inhibition of IFN-gamma and IL-4 signaling in vivo

Citation
T. Naka et al., SOCS-1/SSI-1-deficient NKT cells participate in severe hepatitis through dysregulated cross-talk inhibition of IFN-gamma and IL-4 signaling in vivo, IMMUNITY, 14(5), 2001, pp. 535-545
Citations number
50
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Immunology
Journal title
IMMUNITY
ISSN journal
1074-7613 → ACNP
Volume
14
Issue
5
Year of publication
2001
Pages
535 - 545
Database
ISI
SICI code
1074-7613(200105)14:5<535:SNCPIS>2.0.ZU;2-8
Abstract
Suppressor of cytokine signaling-1 (SOCS-1), also known as STAT-induced STA T inhibitor-1 (SSI-1), is a negative feedback molecule for cytokine signali ng, and its in vivo deletion induces fulminant hepatitis. However, eliminat ion of the STAT1 or STAT6 gene or deletion of NKT cells substantially preve nted severe hepatitis in SOCS-1-deficient mice, while administration of IFN -gamma and IL-4 accelerated its development. SOCS-1 deficiency not only sus tained IFN-gamma /lL-4 signaling but also eliminated the cross-inhibitory a ction of IFN-gamma on IL-4 signaling. These results suggest that SOCS-1 def iciency-induced persistent activation of STAT1 and STAT6, which would be in hibited by SOCS-1 under normal conditions, may induce abnormal activation o f NKT cells, thus leading to lethal pathological changes in SOCS-1-deficien t mice.