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

23 Citations (Scopus)

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

Fingerprint

Interleukin-17
Virus Diseases
Lymphocytes
T-Lymphocytes
Liver
Adenoviridae Infections
Cytokines
Lymphocytic choriomeningitis virus
Biological Therapy
T-Lymphocyte Subsets
Allergy and Immunology
Hepatitis

ASJC Scopus subject areas

  • Immunology

Cite this

Intrahepatic innate lymphoid cells secrete IL-17A and IL-17F that are crucial for T cell priming in viral infection. / Jie, Zuliang; Liang, Yuejin; Hou, Lifei; Dong, Chen; Iwakura, Yoichiro; Soong, Lynn; Cong, Yingzi; Sun, Jiaren.

In: Journal of Immunology, Vol. 192, No. 7, 01.04.2014, p. 3289-3300.

Research output: Contribution to journalArticle

@article{c55be7be92034c7a807dbead7d9a47a5,
title = "Intrahepatic innate lymphoid cells secrete IL-17A and IL-17F that are crucial for T cell priming in viral infection",
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.",
author = "Zuliang Jie and Yuejin Liang and Lifei Hou and Chen Dong and Yoichiro Iwakura and Lynn Soong and Yingzi Cong and Jiaren Sun",
year = "2014",
month = "4",
day = "1",
doi = "10.4049/jimmunol.1303281",
language = "English (US)",
volume = "192",
pages = "3289--3300",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "7",

}

TY - JOUR

T1 - Intrahepatic innate lymphoid cells secrete IL-17A and IL-17F that are crucial for T cell priming in viral infection

AU - Jie, Zuliang

AU - Liang, Yuejin

AU - Hou, Lifei

AU - Dong, Chen

AU - Iwakura, Yoichiro

AU - Soong, Lynn

AU - Cong, Yingzi

AU - Sun, Jiaren

PY - 2014/4/1

Y1 - 2014/4/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84897483592&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84897483592&partnerID=8YFLogxK

U2 - 10.4049/jimmunol.1303281

DO - 10.4049/jimmunol.1303281

M3 - Article

C2 - 24600029

AN - SCOPUS:84897483592

VL - 192

SP - 3289

EP - 3300

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 7

ER -