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10.1002/hep.27392

http://scihub22266oqcxt.onion/10.1002/hep.27392
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suck abstract from ncbi


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pmid25351459      Hepatology 2014 ; 60 (6): 2027-39
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  • IL30 (IL27p28) attenuates liver fibrosis through inducing NKG2D-Rae1 interaction between NKT and activated hepatic stellate cells #MMPMID25351459
  • Mitra A; Satelli A; Yan J; Xueqing X; Gagea M; Hunter CA; Mishra L; Li S
  • Hepatology 2014[Dec]; 60 (6): 2027-39 PMID25351459show ga
  • 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) mixed with corn oil at a ratio 1:3 was injected intraperitoneally (IP) 1µl/gm body weight twice per week for 1 month 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 hydrodynamically 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. Immunophenotyping and knockout studies showed that IL30 recruits NKT cells to the liver to decrease activated hepatic stellate cells (HSCs) significantly and ameliorate liver fibrosis. Both flow cytometric and antibody mediated neutralization studies showed NKT cells alleviate liver fibrosis in an NKG2D dependent manner. Furthermore, chronic treatment with CCl4 showed inducible surface expression of the NKG2D ligand Rae1 on activated HSCs as compared to quiescent ones.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.
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