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

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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

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Interleukin-17
Adaptive Immunity
Hepatitis
Interleukin-7
T-Lymphocytes
Liver
Interleukin-23
Hepatocytes
Th1 Cells
Interleukins
Virus Diseases
Adenoviridae
Immunity
Wounds and Injuries
Infection

ASJC Scopus subject areas

  • Immunology

Cite this

Early IL-17 production by intrahepatic T cells is important for adaptive immune responses in viral hepatitis. / Hou, Lifei; Jie, Zuliang; Desai, Mayura; Liang, Yuejin; Soong, Lynn; Wang, Tian; Sun, Jiaren.

In: Journal of Immunology, Vol. 190, No. 2, 15.01.2013, p. 621-629.

Research output: Contribution to journalArticle

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