Skip to content
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Menu
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Menu
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
immunology and microbiology
IL-17A plays a critical role in the pathogenesis of liver fibrosis through hepatic stellate cell activation
Journal of Immunology, Volume 191, No. 4, Year 2013
Notification
URL copied to clipboard!
Description
Liver fibrosis is a severe, life-threatening clinical condition resulting from nonresolving hepatitis of different origins. IL-17A is critical in inflammation, but its relation to liver fibrosis remains elusive. We find increased IL-17A expression in fibrotic livers from HBV-infected patients undergoing partial hepatectomy because of cirrhosis-related early-stage hepatocellular carcinoma in comparison with control nonfibrotic livers from uninfected patients with hepatic hemangioma. In fibrotic livers, IL-17A immunoreactivity localizes to the inflammatory infiltrate. In experimental carbon tetrachloride-induced liver fibrosis of IL-17RA-deficient mice, we observe reduced neutrophil influx, proinflammatory cytokines, hepatocellular necrosis, inflammation, and fibrosis as compared with control C57BL/6 mice. IL-17A is produced by neutrophils and T lymphocytes expressing the Th17 lineage-specific transcription factor Retinoic acid receptor-related orphan receptor γt. Furthermore, hepatic stellate cells (HSCs) isolated from naive C57BL/6 mice respond to IL-17A with increased IL-6, α-smooth muscle actin, collagen, and TGF-β mRNA expression, suggesting an IL-17A-driven fibrotic process. Pharmacologic ERK1/2 or p38 inhibition significantly attenuated IL- 17A-induced HSC activation and collagen expression. In conclusion, IL-17A+ Retinoic acid receptor-related orphan receptor γt+ neutrophils and T cells are recruited into the injured liver driving a chronic, fibrotic hepatitis. IL-17A-dependent HSC activation may be critical for liver fibrosis. Thus, blockade of IL-17A could potentially benefit patients with chronic hepatitis and liver fibrosis. © 2013 by The American Association of Immunologists, Inc.
Authors & Co-Authors
Tan, Zhongming
China, Nanjing
Nanjing Medical University
China, Beijing
Ministry of Health of People's Republic of China
France, Orleans
Université D'orléans
South Africa, Cape Town
University of Cape Town
Qian, Xiaofeng
China, Nanjing
Nanjing Medical University
China, Beijing
Ministry of Health of People's Republic of China
Jiang, Runqiu
China, Nanjing
Nanjing Medical University
China, Beijing
Ministry of Health of People's Republic of China
Liu, Qianghui
China, Nanjing
Nanjing Medical University
China, Beijing
Ministry of Health of People's Republic of China
Wang, Youjing
China, Nanjing
Nanjing Medical University
China, Beijing
Ministry of Health of People's Republic of China
Chen, Chen
China, Nanjing
Nanjing Medical University
China, Beijing
Ministry of Health of People's Republic of China
Wang, Xuehao
China, Nanjing
Nanjing Medical University
China, Beijing
Ministry of Health of People's Republic of China
Ryffel, Bernhard
France, Orleans
Université D'orléans
South Africa, Cape Town
University of Cape Town
Sun, Beicheng
China, Nanjing
Nanjing Medical University
China, Beijing
Ministry of Health of People's Republic of China
Statistics
Citations: 262
Authors: 9
Affiliations: 4
Identifiers
Doi:
10.4049/jimmunol.1203013
ISSN:
00221767
e-ISSN:
15506606
Research Areas
Cancer
Environmental
Infectious Diseases