Journal of Liver

IL30: A biological cytokine provides hepatic protection in Chronic inflammation mediated liver fibrosis

World Congress on Hepatitis

July 20-22, 2015 Orlando, Florida, USA

Abhisek Mitra

Posters-Accepted Abstracts: J Liver

Abstract:

Chronic hepatic diseases such as cirrhosis, hepatocellular carcinoma and virus mediated immunopathogenic infections are affecting billions of people worldwide. These diseases commonly initiate with fibrosis. Owing to the various side effects of anti-fibrotic therapy and the difficulty of diagnosing asymptomatic patients, suitable medication remains a major concern. To overcome this drawback, the use of cytokine-based sustained therapy might be a suitable alternative with minimal side effects. Here, we studied the therapeutic efficacy and potential mechanisms of IL30 as anti-fibrosis therapy in murine liver fibrosis models. Carbon tetrachloride (CCl4) or 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) 0.1% (wt/wt) Purnima 5015 Chow was fed for 3 weeks to induce liver fibrosis. Either control vector (pCtr) or pIL30 was injected hydro-dynamically once per week. A significant decrease in collagen deposition and reduced expression of ?-smooth muscle Actin (?SMA) protein indicated that IL30?based gene therapy dramatically reduced bridging fibrosis that was induced by CCl4 or DDC. Immuno phenotyping and knockout studies showed that IL30 recruits NKT cells to the liver to remove activated hepatic stellate cells (HSCs) significantly and ameliorate liver fibrosis. Both flow cytometric and antibody mediated neutralization studies showed liver NKT cells up-regulates NKG2D ligand and it binds with the NKG2D ligand Rae1 positive activated HSCs to ameliorate liver fibrosis. Furthermore, adoptive transfer of liver NKT cells in T cells deficient mice showed reduction of fibrosis upon IL30 administration. Taken together, our results show that highly target specific liver NKT cells selectively remove activated HSCs via an NKG2D-Rae1 interaction to ameliorate liver fibrosis after IL30 treatment.