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    Immune Cell Profiling of IFN-[lambda] Response Shows pDCs Express Highest Level of IFN-[lambda]R1 and Are Directly Responsive via the JAK-STAT Pathway


    Kelly, Aoife and Robinson, Mark W. and Roche, Gerard and Biron, Christine A. and O'Farrelly, Cliona and Ryan, Elizabeth J. (2016) Immune Cell Profiling of IFN-[lambda] Response Shows pDCs Express Highest Level of IFN-[lambda]R1 and Are Directly Responsive via the JAK-STAT Pathway. Journal of Interferon & Cytokine Research, 36 (12). pp. 671-680. ISSN 1557-7465

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    Abstract

    The interferon lambda (IFN-l) cytokines have well-known antiviral properties, yet their contribution to immune regulation is not well understood. Epithelial cells represent the major target cell of IFN-l; peripheral blood mononuclear cells are generally considered nonresponsive, with the exception of plasmacytoid dendritic cells (pDCs). In this study we aimed to define the potential for discrete subpopulations of cells to directly respond to IFN-l. Analysis of peripheral blood leukocytes reveals that, while pDCs uniformly express the highest levels of IFN-l receptor, a small proportion of B cells and monocytes also express the receptor. Nevertheless, B cells and monocytes respond poorly to IFN-l stimulation in vitro, with minimal STAT phosphorylation and interferonstimulated gene (ISG) induction observed. We confirm that pDCs respond to IFN-l in vitro, upregulating their expression of pSTAT1, pSTAT3, and pSTAT5. However, we found that pDCs do not upregulate pSTAT6 in response to IFN-l treatment. Our results highlight unique aspects of the response to IFN-l and confirm that while the IFN-l receptor is expressed by a small proportion of several different circulating immune cell lineages, under normal conditions only pDCs respond to IFN-l stimulation with robust STAT phosphorylation and ISG induction. The difference in STAT6 responsiveness of pDCs to type I and type III interferons may help explain the divergence in their biological activities.

    Item Type: Article
    Additional Information: Cite as: Kelly A, Robinson MW, Roche G, Biron CA, O'Farrelly C, Ryan EJ. Immune Cell Profiling of IFN-λ Response Shows pDCs Express Highest Level of IFN-λR1 and Are Directly Responsive via the JAK-STAT Pathway. J Interferon Cytokine Res. 2016;36(12):671-680. doi:10.1089/jir.2015.0169. Funding: This study was supported by Science Foundation Ireland (grant # 12/IA/1667) and the Irish Health Research Board (grant # TRA/2007/14). Prof. Christine Biron is supported by the National Institutes of Health, USA.
    Keywords: Type III IFNs; JAK-STAT; peripheral blood mononuclear cells; dendritic cells;
    Academic Unit: Faculty of Science and Engineering > Biology
    Item ID: 13683
    Identification Number: https://doi.org/10.1089/jir.2015.0169
    Depositing User: Mark Robinson
    Date Deposited: 27 Nov 2020 17:13
    Journal or Publication Title: Journal of Interferon & Cytokine Research
    Publisher: Mary Ann Liebert, Inc.
    Refereed: Yes
    Funders: Science Foundation Ireland (SFI), Health Research Board (HRB)
    URI:

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