Format

Send to

Choose Destination
Innate Immun. 2014 Aug;20(6):598-605. doi: 10.1177/1753425913503385. Epub 2013 Sep 17.

IFNL3 mediates interaction between innate immune cells: Implications for hepatitis C virus pathogenesis.

Author information

1
Institute for Immunology and Allergy Research, Westmead Millennium Institute, University of Sydney, Sydney, Australia koco2654@uni.sydney.edu.au.
2
Storr Liver Unit, Westmead Millennium Institute and Westmead Hospital, University of Sydney, Sydney, Australia.
3
Institute for Immunology and Allergy Research, Westmead Millennium Institute, University of Sydney, Sydney, Australia Storr Liver Unit, Westmead Millennium Institute and Westmead Hospital, University of Sydney, Sydney, Australia.
4
Institute for Immunology and Allergy Research, Westmead Millennium Institute, University of Sydney, Sydney, Australia.
5
Storr Liver Unit, Westmead Millennium Institute and Westmead Hospital, University of Sydney, Sydney, Australia Centre for Infectious Diseases and Microbiology, Sydney Emerging infections and Biosecurity Institute, University of Sydney and Westmead Hospital, Sydney Australia.
6
Department of Gastroenterology and Hepatology, Nepean Hospital, Sydney Australia.

Abstract

Common IFN lambda 3 (IFNL3) variants have been demonstrated to affect spontaneous and treatment-induced clearance of hepatitis C virus (HCV) infection. The functional basis of these genetic variants has yet to be determined. Data examining the effect of IFNL3, specifically, in innate immune cells is lacking. Here, we determined the expression of IFNL3 and its receptor IFNLR1 in blood immune cell subsets and in HCV-infected livers. Next we assessed their sensitivity to IFNL3. All participants were genotyped for the IFNL3 SNPs rs8099917 and rs12979860. Importantly, unstimulated blood immune cells express significantly higher levels of IFNL3 than HCV liver biopsies. Plasmacytoid dendritic cells (pDCs) are the predominant producers of IFNLR1, especially in response to IFN-α. PBMCs, monocytes and pDCs all respond to IFNL3 based on MxA up-regulation. No differences in IFNL3 expression levels between rs8099917 or rs12979860 genotypes were detected. This is the first study to show peripheral blood pDCs to be the main producers of IFNL3, especially compared with HCV-infected livers. This makes innate immune cells the key players in determining the functional significance of INFL3 polymorphisms in patients with HCV.

KEYWORDS:

IFN; IFNL3; hepatitis C; innate immunity

PMID:
24045339
DOI:
10.1177/1753425913503385
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Atypon
Loading ...
Support Center