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dc.rights.licenseAttribution 4.0 International (CC BY 4.0)
dc.creatorBowen, Kelly E.
dc.creatorMathew, Stephen O.
dc.creatorBorgmann, Kathleen
dc.creatorGhorpade, Anuja
dc.creatorMathew, Porunelloor A.
dc.identifier.citationBowen, K. E., Mathew, S. O., Borgmann, K., Ghorpade, A., & Mathew, P. A. (2018). A novel ligand on astrocytes interacts with natural cytotoxicity receptor NKp44 regulating immune response mediated by NK cells. PloS one, 13(2), e0193008.
dc.description.abstractNK cells play important role in immunity against pathogens and cancer. NK cell functions are regulated by inhibitory and activating receptors binding corresponding ligands on the surface of target cells. NK cells were shown to be recruited to the CNS following several pathological conditions. NK cells could impact CNS physiology by killing glial cells and by secreting IFN-gamma. Astrocytes are intimately involved in immunological and inflammatory events occurring in the CNS and reactive astrogliosis is a key feature in HIV-associated neurocognitive disorders. There is little data on NK-astrocyte interactions and ligands expressed on astrocytes that could impact NK cell function. Natural cytotoxicity receptors (NCRs) play a critical role in the cytolytic function of NK cells. Among the NCRs, NKp44 is unique in expression and signal transduction. NKp44 is expressed only upon activation of NK cells and it can mediate both activating and inhibitory signals to NK cells. Here, we have studied the expression and function of natural cytotoxicity receptor NKp44 upon NK-astrocytes interactions in the presence or absence of an HIV peptide (HIV-3S peptide) shown to induce NK cell killing of CD4+ T cells during HIV-infection. Using a fusion protein consisting of the extracellular domain of NKp44 fused to Fc portion of human IgG, we determined the expression of a novel ligand for NKp44 (NKp44L) on astrocytes. Incubation of astrocytes with HIV-3S peptide downregulated NKp44L expression on astrocytes implicating protection from NK mediated killing. Thus, our study showed that NKp44 have a protective effect on astrocytes from NK cell mediated killing during HIV infection and impact astrocyte role in HAND.
dc.description.sponsorshipThis work was supported by a grant from National Institute of Health (NS101481) and UNTHSC Seed Grant. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
dc.sourcePLoS One
dc.subject.meshAstrocytes / immunology
dc.subject.meshAstrocytes / metabolism
dc.subject.meshCells, Cultured
dc.subject.meshCoculture Techniques
dc.subject.meshCytotoxicity, Immunologic
dc.subject.meshHIV Infections / metabolism
dc.subject.meshHuman Immunodeficiency Virus Proteins / metabolism
dc.subject.meshInterferon-gamma / metabolism
dc.subject.meshKiller Cells, Natural / immunology
dc.subject.meshMiddle Aged
dc.subject.meshNatural Cytotoxicity Triggering Receptor 2 / antagonists & inhibitors
dc.subject.meshNatural Cytotoxicity Triggering Receptor 2 / metabolism
dc.titleA novel ligand on astrocytes interacts with natural cytotoxicity receptor NKp44 regulating immune response mediated by NK cells
dc.rights.holderCopyright © 2018 Bowen et al
dc.creator.orcid0000-0003-0897-390X (Borgmann, Kathleen)
dc.creator.orcid0000-0001-8137-0895 (Mathew, Porunelloor)
dc.creator.orcid0000-0001-5784-224X (Mathew, Stephen)

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Attribution 4.0 International (CC BY 4.0)
Except where otherwise noted, this item's license is described as Attribution 4.0 International (CC BY 4.0)