We read with interest the article by Torisu et al. on the protective role of suppressor of cytokine signaling-1 (SOCS1), a negative-feedback molecule for cytokine signaling, in concanavalin A (ConA)-induced hepatitis.1 The authors observed that hepatocyte-specific SOCS1-conditional knockout (L-SOCS1 cKO) mice showed enhanced ConA-induced hepatitis compared with wild-type mice. They also found that proapoptotic signals, including signal transducers and activators of transcription 1 (STAT1), Jun-terminal kinase (JNK) activation, and Fas expression were also elevated in L-SOCS1 cKO mice. The authors attribute the mechanism to the prevention of Fas and tumor necrosis factor-α–induced hepatocyte apoptosis.
SOCS1 is a known inhibitor of cytokine signaling pathways and has been shown to be a regulator of immune tolerance. T cells from SOCS1−/− mice can proliferate after anti–T cell receptor stimulation in the absence of interleukin-2 (IL-2) or anti-CD28 costimulatory signals.2 In addition, SOCS1 expression is very high in CD4+CD25+ regulatory T cells (Tregs), which has led to the possibility that SOCS1 is involved in Treg function.3 Indeed, the suppressive activity of SOCS1-deficient Tregs is less than that of wild-type Tregs.4
Recently, Tregs were found to mediate the tolerance in ConA-induced hepatitis.5 This suppressive effect was caused by the induction of IL-10 produced by Tregs and the accompanying inhibition of IL-2. However, the mechanisms by which Tregs induce tolerance and alleviate liver injury in ConA-induced hepatitis still remain to be elucidated.
In addition, it is well known that Con A-induced liver injury is mainly caused by the accumulation of activated T cells and natural killer T cells, which is the result of dysfunction of Tregs. So, further research should be carried out to investigate SOCS1 functions of Tregs in ConA-induced hepatitis. These studies will not only improve our knowledge about the molecular mechanism of Treg function in hepatitis, but also bring great benefits to the treatment and prevention of liver diseases.