RGD Reference Report - Type III interferons, IL-28 and IL-29, are increased in chronic HCV infection and induce myeloid dendritic cell-mediated FoxP3+ regulatory T cells. - Rat Genome Database

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Type III interferons, IL-28 and IL-29, are increased in chronic HCV infection and induce myeloid dendritic cell-mediated FoxP3+ regulatory T cells.

Authors: Dolganiuc, Angela  Kodys, Karen  Marshall, Christopher  Saha, Banishree  Zhang, Shuye  Bala, Shashi  Szabo, Gyongyi 
Citation: Dolganiuc A, etal., PLoS One. 2012;7(10):e44915. doi: 10.1371/journal.pone.0044915. Epub 2012 Oct 10.
RGD ID: 126848749
Pubmed: PMID:23071503   (View Abstract at PubMed)
PMCID: PMC3468613   (View Article at PubMed Central)
DOI: DOI:10.1371/journal.pone.0044915   (Journal Full-text)


BACKGROUND & AIMS: Hepatitis C virus (HCV) is difficult to eradicate and type III interferons (IFN-λ, composed of IL-28A, IL-28B and IL-29) are novel therapeutic candidates. We hypothesized that IFN-λ have immunomodulatory effects in HCV- infected individuals.
MATERIALS AND METHODS: We analyzed the expression of IFN-λ and its receptor (composed of IL-10R2 and IFN-λR subunits) in the blood and livers of patients with chronic (c)HCV infection compared to controls (those who cleared HCV by sustained virological response, SVR, and those with liver inflammation of non-viral origin, non-alcoholic steatohepatitis, NASH). We also compared the proliferative capacity of dendritic cells (DCs) obtained from healthy individuals and those with chronic HCV using a mixed leukocyte reaction combined with 3H-Td incorporation. In addition, the composition of the IFN-λ receptor (IFN-λR) on myeloid DCs, plasmacytoid DCs, PBMCs, and T cells was determined by FACS analysis.
RESULTS: We report that the expression of IFN-λ protein in serum and mRNA in liver is increased in cHCV patients, but not in those with HCV SVR or NASH, compared to controls. Liver level of IFN-λR mirrored the expression of serum IFN-λ and was higher in cHCV, compared to controls and HCV-SVR patients, suggesting that elevation of IFN-λ and IFN-λR are HCV-dependent. We further identified that innate immune cell populations expressed complete IFN-λ receptor. In vitro, recombinant IFN-λ promoted differentiation of monocyte-derived dendritic cells (DCs) into a phenotype with low T cell stimulatory capacity and high PD-L1 expression, which further promoted expansion of existing regulatory T cells. IFN-λ-DCs failed to induce de novo generation of regulatory T cells. The inhibitory capacity of IFN-λ-DCs was counteracted by recombinant IL-12 and by neutralization of the PD-1/PD-L1 system.
CONCLUSIONS: Our novel findings of the immunomodulatory effect of IFN-λ contribute to the understanding of the anti-inflammatory and/or anti-viral potential of IFN-λ in cHCV.



RGD Manual Disease Annotations    Click to see Annotation Detail View
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
IFNL1HumanChronic Hepatitis C  IEP mRNA more ...RGD 
Ifnl1RatChronic Hepatitis C  ISOIFNL1 (Homo sapiens)mRNA more ...RGD 

Objects Annotated

Genes (Rattus norvegicus)
Ifnl1  (interferon, lambda 1)

Genes (Homo sapiens)
IFNL1  (interferon lambda 1)


Additional Information