| First Author | Hou L | Year | 2013 |
| Journal | J Immunol | Volume | 190 |
| Issue | 2 | Pages | 621-9 |
| PubMed ID | 23233727 | Mgi Jnum | J:191047 |
| Mgi Id | MGI:5460897 | Doi | 10.4049/jimmunol.1201970 |
| Citation | Hou L, et al. (2013) Early IL-17 Production by Intrahepatic T Cells Is Important for Adaptive Immune Responses in Viral Hepatitis. J Immunol 190(2):621-9 |
| abstractText | This study was conducted to examine the interactions among the innate and adaptive immune components of the liver parenchyma during acute viral hepatitis. Mice were i.v. infected with a recombinant adenovirus, and within the first 24 h of infection, we found a transient but significant accumulation of IL-17 and IL-23 in the liver. In vivo neutralization of these interleukins alleviated the liver injury. Further investigations showed that IL-17 neutralization halted the intrahepatic accumulation of CTLs and Th1 cells. A majority of the IL-17-producing cells in the liver were gammadelta T cells. Additionally, intrahepatic IL-17(+) gammadelta T cells, but not the IFN-gamma(+) ones, preferentially expressed IL-7Ralpha (CD127) on their surface, which coincided with an elevation of hepatocyte-derived IL-7 at 12 h postinfection. IL-7Ralpha blockade in vivo severely impeded the expansion of IL-17-producing cells after viral infection. In vitro, IL-7 synergized with IL-23 and directly stimulated IL-17 production from gammadelta T cells in response to TCRgammadelta stimulation. Finally, type I IFN (IFN-I) signaling was found to be critical for hepatic IL-7 induction. Collectively, these results showed that the IFN-I/IL-7/IL-17 cascade was important in priming T cell responses in the liver. Moreover, the highly coordinated cross talk among hepatocytes and innate and adaptive immune cells played a critical role in anti-viral immunity in hepatitis. |
