Endogenous IL-33 Deficiency Exacerbates Liver Injury and Increases Hepatic Influx of Neutrophils in Acute Murine Viral Hepatitis

Virginie Carrière, Muhammad Imran Arshad, Jacques Le Seyec, Benjamin Lefevre, Muhammad Farooq, Aurélien Jan, Christelle Manuel, Laurence Touami-Bernard, Catherine Lucas-Clerc, Valentine Genet, Hugues Gascan, Jean Philippe Girard, Frédéric Chalmel, Lucie Lamontagne, Claire Piquet-Pellorce, Michel Samson*

*المؤلف المقابل لهذا العمل

نتاج البحث: المساهمة في مجلةArticleمراجعة النظراء

9 اقتباسات (Scopus)

ملخص

The alarmin IL-33 has been described to be upregulated in human and murine viral hepatitis. However, the role of endogenous IL-33 in viral hepatitis remains obscure. We aimed to decipher its function by infecting IL-33-deficient mice (IL-33 KO) and their wild-type (WT) littermates with pathogenic mouse hepatitis virus (L2-MHV3). The IL-33 KO mice were more sensitive to L2-MHV3 infection exhibiting higher levels of AST/ALT, higher tissue damage, significant weight loss, and earlier death. An increased depletion of B and T lymphocytes, NKT cells, dendritic cells, and macrophages was observed 48 h postinfection (PI) in IL-33 KO mice than that in WT mice. In contrast, a massive influx of neutrophils was observed in IL-33 KO mice at 48 h PI. A transcriptomic study of inflammatory and cell-signaling genes revealed the overexpression of IL-6, TNFα, and several chemokines involved in recruitment/activation of neutrophils (CXCL2, CXCL5, CCL2, and CCL6) at 72 h PI in IL-33 KO mice. However, the IFNγ was strongly induced in WT mice with less profound expression in IL-33 KO mice demonstrating that endogenous IL-33 regulated IFNγ expression during L2-MHV3 hepatitis. In conclusion, we demonstrated that endogenous IL-33 had multifaceted immunoregulatory effect during viral hepatitis via induction of IFNγ, survival effect on immune cells, and infiltration of neutrophils in the liver.

اللغة الأصليةEnglish
رقم المقال1359064
دوريةMediators of Inflammation
مستوى الصوت2017
المعرِّفات الرقمية للأشياء
حالة النشرPublished - 2017

ASJC Scopus subject areas

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بصمة

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