Suppressor of cytokine signaling-1 regulates signaling in response to interleukin-2 and other γc-dependent cytokines in peripheral T cells

Abstract

Suppressor of cytokine signaling-1 (SOCS-1) is an essential regulator of cytokine signaling. SOCS-1-/- mice die before weaning with a complex disease characterized by fatty degeneration and necrosis of the liver. This disease is mediated by interferon (IFN) γ as neonatal mortality fails to occur in SOCS-1-/-IFNγ-/- mice. However, the immune system of healthy SOCS-1-/-IFNγ-/- mice is dysregulated with a reduced ratio of CD4:CD8 T cells and increases in some aspects of T cell activation. SOCS-1-/-IFNγ-/- mice also die before their wild type and IFNγ-/- counterparts with a range of inflammatory conditions including pneumonia, gut infiltration, and skin ulceration, suggesting that SOCS-1 control..