Intrahepatic innate lymphoid cells secrete IL-17A and IL-17F that are crucial for T cell priming in viral infection

Zuliang Jie, Yuejin Liang, Lifei Hou, Chen Dong, Yoichiro Iwakura, Lynn Soong, Yingzi Cong, Jiaren Sun

Research output: Contribution to journalArticle

25 Scopus citations

Abstract

Intrahepatic cell-derived, early IL-17 is important for activating APCs in viral infection; however, the source and regulation of this IL-17 surge in the liver microenvironment are not well defined. In this article, we present evidence for a significant expansion of IL- 17A/F-producing cells in mouse liver within 24 h of adenovirus infection. In addition to γδ T cells, a subset of IL-17A/F+ cells expressed no myeloid or lymphoid lineage markers. Instead, they expressed high levels of stem cell markers, IL-7R and RORγt, consistent with the newly described innate lymphoid cells (ILCs). Based on their unique surface markers and cytokine profiles, these cells were confirmed as group 3 ILCs. In addition to adenovirus infection, group 3 ILCs were also found in mouse liver within 24 h of lymphocytic choriomeningitis virus infection. They contributed significantly to the establishment of the early cytokine milieu in virusinfected liver. Functional studies with mice deficient of IL-17R, IL-17A, and IL-17F further revealed that IL-17 signaling was critical for priming T cell responses in viral hepatitis. IL-17A repressed IL-17F secretion in vitro and in vivo; IL-17F+ intrahepatic cells expanded more vigorously in IL-17A knockout animals, permitting efficient Ag presentation and T cell function. However, IL-17F neither inhibited IL-17A in vitro nor regulated its secretion in vivo. Together, this study has demonstrated the importance of a unique intrahepatic subpopulation and subsequent IL-17A/F regulation at initial stages of viral infection in the liver. These results have important implications for anticytokine biologic therapy and vaccine development. The Journal of Immunology, 2014, 192: 3289-3300.

Original languageEnglish (US)
Pages (from-to)3289-3300
Number of pages12
JournalJournal of Immunology
Volume192
Issue number7
DOIs
StatePublished - Apr 1 2014

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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