Early IL-17 production by intrahepatic T cells is important for adaptive immune responses in viral hepatitis

Lifei Hou, Zuliang Jie, Mayura Desai, Yuejin Liang, Lynn Soong, Tian Wang, Jiaren Sun

Research output: Contribution to journalArticlepeer-review

45 Scopus citations

Abstract

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 γδ T cells. Additionally, intrahepatic IL-17+ γδ T cells, but not the IFN-γ+ ones, preferentially expressed IL-7Rα (CD127) on their surface, which coincided with an elevation of hepatocyte-derived IL-7 at 12 h postinfection. IL-7Rα 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 γδ T cells in response to TCRγδ 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.

Original languageEnglish (US)
Pages (from-to)621-629
Number of pages9
JournalJournal of Immunology
Volume190
Issue number2
DOIs
StatePublished - Jan 15 2013

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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