title: HMBOX1 negatively regulates NK cell functions by suppressing the NKG2D/DAP10 signaling pathway.
abstract: HMBOX1 is a new member of the homeobox family. Homeobox members have been reported to participate in embryonic development and systemic metabolism, but the function of HMBOX1 remains unclear, especially in the hematopoietic system. Here, we show that HMBOX1 is expressed at a high level in primary human NK cells but is expressed at much lower levels in NK cell lines. Overexpression of HMBOX1 significantly inhibited NK cell activities, including natural cytotoxicity against tumor cells, the level of CD107a (a marker protein for degranulation) and the production of cytolytic proteins (perforin and granzymes). More interestingly, HMBOX1 negatively regulated the expression of NKG2D and the activation of the NKG2D/DAP10 signaling pathway in NK cells. This effect was reversed by knocking down HMBOX1. Taken together, these findings demonstrate that HMBOX1 may act as a negative regulator of NK cell functions via suppressing the NKG2D/DAP10 signaling pathway.
authors.affiliation: School of Pharmaceutical Sciences, Shandong University, Jinan, China.
authors.forename: Longyan
authors.initials: L
authors.lastname: Wu
authors.forename: Cai
authors.initials: C
authors.lastname: Zhang
authors.forename: Jian
authors.initials: J
authors.lastname: Zhang
mesh_terms: D015550:Cell Degranulation / Q000276:immunology; D045744:Cell Line, Tumor; D003602:Cytotoxicity, Immunologic / Q000235:genetics*; D005434:Flow Cytometry; D015870:Gene Expression / Q000276:immunology; D020868:Gene Silencing / Q000187:drug effects; D053804:Granzymes / Q000096:biosynthesis; D018398:Homeodomain Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007113:Immunity, Innate; D007694:Killer Cells, Natural / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D052118:Lysosomal-Associated Membrane Protein 1 / Q000096:biosynthesis; D055655:NK Cell Lectin-Like Receptor Subfamily K / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D054353:Perforin / Q000096:biosynthesis; D061251:Primary Cell Culture; D034741:RNA, Small Interfering / Q000494:pharmacology; D060888:Real-Time Polymerase Chain Reaction; D011971:Receptors, Immunologic / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology*
chemical_list: C120528:HCST protein, human; C512050:HMBOX1 protein, human; D018398:Homeodomain Proteins; C527085:KLRK1 protein, human; D052118:Lysosomal-Associated Membrane Protein 1; D055655:NK Cell Lectin-Like Receptor Subfamily K; D034741:RNA, Small Interfering; D011971:Receptors, Immunologic; D054353:Perforin; D053804:Granzymes