[PDF][PDF] Interleukin 22 (IL‐22) plays a protective role in T cell‐mediated murine hepatitis: IL‐22 is a survival factor for hepatocytes via STAT3 activation

S Radaeva, R Sun, H Pan, F Hong, B Gao - Hepatology, 2004 - Wiley Online Library
S Radaeva, R Sun, H Pan, F Hong, B Gao
Hepatology, 2004Wiley Online Library
The central role of T cell activation in hepatocellular injury has been well documented. In this
article, we provide evidence suggesting that T cells may also play a protective role in liver
disease by releasing interleukin‐22 (IL‐22), a recently identified T cell‐derived cytokine
whose biological significance is unclear. IL‐22 messenger RNA and protein expression are
significantly elevated in T cell‐mediated hepatitis induced by concanavalin A (ConA) but are
less extensively elevated in the carbon tetrachloride‐induced liver injury model. Activated …
Abstract
The central role of T cell activation in hepatocellular injury has been well documented. In this article, we provide evidence suggesting that T cells may also play a protective role in liver disease by releasing interleukin‐22 (IL‐22), a recently identified T cell‐derived cytokine whose biological significance is unclear. IL‐22 messenger RNA and protein expression are significantly elevated in T cell‐mediated hepatitis induced by concanavalin A (ConA) but are less extensively elevated in the carbon tetrachloride‐induced liver injury model. Activated CD3+ T cells are likely responsible for the production of IL‐22 in the liver after injection of ConA. The IL‐22 receptor is normally expressed at high levels by hepatocytes and further induced after ConA injection. IL‐22 blockade with a neutralizing antibody reduces signal transducer and activator of transcription factor 3 (STAT3) activation and worsens liver injury in T cell‐mediated hepatitis, whereas injection of recombinant IL‐22 attenuates such injury. In vitro treatment with recombinant IL‐22 or overexpression of IL‐22 promotes cell growth and survival in human hepatocellular carcinoma HepG2 cells. Stable overexpression of IL‐22 in HepG2 cells constitutively activates STAT3 and induces expression of a variety of antiapoptotic (e.g., Bcl‐2, Bcl‐xL, Mcl‐1) and mitogenic (e.g., c‐myc, cyclin D1, Rb2, CDK4) proteins. Blocking STAT3 activation abolishes the antiapoptotic and mitogenic actions of IL‐22 in hepatic cells. In conclusion, the T cell‐derived cytokine IL‐22 is a survival factor for hepatocytes; this suggests that T cell activation may also prevent and repair liver injury by releasing hepatoprotective cytokine IL‐22 in addition to its previously documented central role in hepatocellular injury. (HEPATOLOGY 2004;39:1332–1342.)
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