IL-33 induces nuocytes and modulates liver injury in viral hepatitis

Yuejin Liang, Zuliang Jie, Lifei Hou, Renan Aguilar-Valenzuela, David Vu, Lynn Soong, Jiaren Sun

Research output: Contribution to journalArticle

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Abstract

Molecules containing damage-associated molecular patterns play an important role in many pathogenic processes. In this study, our aim was to investigate the role of IL-33, a damage-associated molecular pattern molecule, in adenovirus (Ad)-induced liver inflammation. Ad-infected mice exhibited a steadily increased IL-33 and its receptor IL-1R-like 1 expression in the liver during the first week of infection. Treatment of exogenous IL-33 resulted in a great decrease in the serum alanine aminotransferase levels and the number of Councilman bodies in the liver. Attenuated liver injury by IL-33 correlated with an increase in T regulatory cells but with a decrease in macrophages, dendritic cells, and NK cells in the liver. IL-33 enhanced both type 1 (IL-2 and IFN-γ) and type 2 (IL-5 and IL-13) immune responses in infected mice. However, IL-33 inhibited TNF-α expression in hepatic T cells and macrophages, and significantly reduced TNF-α levels in the liver. We found that in addition to its direct effects, IL-33 strongly induced novel nuocytes in the livers and spleens of infected mice. When cocultured with nuocytes, hepatic T cells and macrophages expressed lower levels of TNF-α. The IL-33-treated mice also demonstrated a slight delay, but no significant impairment, in eliminating an intrahepatic infection with Ad. In conclusion, this study reveals that IL-33 acts as a potent immune stimulator and a hepatoprotective cytokine in acute viral hepatitis. Its direct immunoregulatory functions and ability to induce novel nuocytes further suggest to us that it may be a potentially promising therapeutic candidate for the management of viral hepatitis.

Original languageEnglish (US)
Pages (from-to)5666-5675
Number of pages10
JournalJournal of Immunology
Volume190
Issue number11
DOIs
StatePublished - Jun 1 2013

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Hepatitis
Liver
Wounds and Injuries
Macrophages
Adenoviridae
Hepatocytes
T-Lymphocytes
Adenoviridae Infections
Interleukin-33
Interleukin-13
Interleukin-5
Regulatory T-Lymphocytes
Alanine Transaminase
Natural Killer Cells
Dendritic Cells
Interleukin-2
Spleen
Cytokines
Inflammation
Infection

ASJC Scopus subject areas

  • Immunology

Cite this

IL-33 induces nuocytes and modulates liver injury in viral hepatitis. / Liang, Yuejin; Jie, Zuliang; Hou, Lifei; Aguilar-Valenzuela, Renan; Vu, David; Soong, Lynn; Sun, Jiaren.

In: Journal of Immunology, Vol. 190, No. 11, 01.06.2013, p. 5666-5675.

Research output: Contribution to journalArticle

Liang, Yuejin ; Jie, Zuliang ; Hou, Lifei ; Aguilar-Valenzuela, Renan ; Vu, David ; Soong, Lynn ; Sun, Jiaren. / IL-33 induces nuocytes and modulates liver injury in viral hepatitis. In: Journal of Immunology. 2013 ; Vol. 190, No. 11. pp. 5666-5675.
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