Journal article
IFN-α-Induced Downregulation of miR-221 in Dendritic Cells: Implications for HCV Pathogenesis and Treatment
Journal of interferon & cytokine research, v 35(9), pp 698-709
01 Sep 2015
PMID: 26090579
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Although interferon (IFN)-α is known to exert immunomodulatory and antiproliferative effects on dendritic cells (DCs) through induction of protein-coding IFN-stimulated genes (ISGs), little is known about IFN-α-regulated miRNAs in DCs. Since several miRNAs are involved in regulating DC functions, it is important to investigate whether IFN-α's effects on DCs are mediated through miRNAs as well. In this study, we examined miRNA expression patterns in myeloid DCs (mDCs) and plasmacytoid DCs after exposing them to IFN-α. We report that IFN-α downregulates miR-221 in both DC subsets via inhibition of STAT3. We validated proapoptotic proteins BCL2L11 and CDKN1C as miR-221 targets suggesting that IFN-α can induce DC apoptosis via miR-221 downregulation. In addition, we validated another miR-221 target, SOCS1, which is known to be a negative regulator of JAK/STAT signaling. Consistent with this, miR-221 overexpression in mDCs enhanced the secretion of proinflammatory cytokines IL-6 and TNF-α. In peripheral blood mononuclear cells (PBMCs) of HIV-1/HCV co-infected individuals undergoing IFN-α-based treatment the baseline miR-221 expression was lower in non-responders compared with responders; and miR-221 expression directly correlated with DC frequency and IL-6/TNF-α secretion. In addition to PBMCs, we isolated total liver cells and kupffer cells from HCV-infected individuals and individuals with alcoholic cirrhosis. We found that both total liver cells and kupffer cells from HCV-infected individuals had significantly higher miR-221 levels compared with individuals with cirrhosis. Overall, we demonstrate that IFN-α exerts both antiproliferative and immunomodulatory effects on mDCs via miR-221 downregulation; and IFN-miR-221 axis can play important role in HCV pathogenesis and treatment.
Metrics
Details
- Title
- IFN-α-Induced Downregulation of miR-221 in Dendritic Cells: Implications for HCV Pathogenesis and Treatment
- Creators
- Mohit Sehgal - 1Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, PennsylvaniaMarija Zeremski - 2Weill Cornell Medical College, New York, New YorkAndrew H Talal - 3School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, New YorkRashida Ginwala - 1Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, PennsylvaniaElizabeth Elrod - 4Emory Vaccine Center, Atlanta, GeorgiaArash Grakoui - 4Emory Vaccine Center, Atlanta, GeorgiaQi-Ging Li - 5Duke University Medical Center, Durham, North CarolinaRamila Philip - 6Immunotope, Inc., Pennsylvania Biotechnology Center, Doylestown, PennsylvaniaZafar K Khan - 1Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, PennsylvaniaPooja Jain - 1Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, Pennsylvania
- Publication Details
- Journal of interferon & cytokine research, v 35(9), pp 698-709
- Publisher
- Mary Ann Liebert, Inc
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Microbiology and Immunology
- Web of Science ID
- WOS:000360590400005
- Scopus ID
- 2-s2.0-84941062364
- Other Identifier
- 991014878265004721
UN Sustainable Development Goals (SDGs)
This publication has contributed to the advancement of the following goals:
InCites Highlights
Data related to this publication, from InCites Benchmarking & Analytics tool:
- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Biochemistry & Molecular Biology
- Cell Biology
- Immunology