Michael Rory Daws

• Bjørnsen, Elisabeth Gyllensten; Thiruchelvam-Kyle, Lavanya; Hoelsbrekken, Sigurd Erik; Henden, Camilla; Sæther, Per Christian; Boysen, Preben; Daws, Michael Rory & Dissen, Erik (2019). B7H6 is a functional ligand for NKp30 in rat and cattle and determines NKp30 reactivity toward human cancer cell lines. European Journal of Immunology.  ISSN 0014-2980.  49(1), s 54- 65 . doi: 10.1002/eji.201847746 Fulltekst i vitenarkiv. Vis sammendrag

  NK cells kill cancer cells and infected cells upon activation by cell surface receptors. Human NKp30 is an activating receptor expressed by all mature NK cells. The B7 family member B7H6 has been identified as one ligand for NKp30. Several alternative ligands have also been reported, and the field remains unsettled. To this end, we have identified full‐length functional B7H6 orthologs in rat and cattle, demonstrated by phylogenetic analysis and transfection experiments. In cell–cell contact‐dependent assays, chimeric NKp30 reporter cells responded strongly to B7H6 in rat and cattle. Likewise, rat NKp30 expressing target cells induced strong activation of B7H6 reporter cells. Together, these observations demonstrate that B7H6 is conserved as a functional ligand for NKp30 in mammalian species separated by more than 100 million years of evolution. B7H6 and NKp30 are pseudogenes in laboratory mice. The rat thus represents an attractive experimental animal model to study the NKp30‐B7H6 interaction in vivo. B7H6 was widely expressed among human cancer cell lines, and the expression level correlated strongly with the activation of human NKp30 reporter cells. Furthermore, siRNA knockdown of B7H6 abolished NKp30 reporter responses, suggesting that B7H6 is the major functionally relevant expressed ligand for NKp30 on these cancer cell lines.

• Daws, Michael Rory; Nakken, Britt; Lobato, Pascual Ana; Josien, Regis; Dissen, Erik & Fossum, Sigbjørn (2019). Dendritic Cell Activating Receptor 1 (DCAR1) Associates With Fc?RI? and Is Expressed by Myeloid Cell Subsets in the Rat. Frontiers in Immunology.  ISSN 1664-3224.  10, s 1060 . doi: 10.3389/fimmu.2019.01060 Vis sammendrag

  Dendritic cell activating receptor-1 (DCAR1) is a cell-surface receptor encoded by the Antigen Presenting Lectin-like gene Complex (APLEC). We generated a mouse monoclonal antibody against rat DCAR1, and used this to characterize receptor expression and function. Rat DCAR1 was expressed on minor subsets of myeloid cells in lymphoid tissue, but was uniformly expressed at a high level by eosinophils, and at a low level by neutrophils. It was expressed by eosinophils in the peritoneal cavity and the lamina propria of the gut, and by subsets of macrophages or dendritic cells at these sites. Polarization of peritoneal macrophages showed that DCAR1 expression was absent on M1 macrophages, and increased on M2 macrophages. DCAR1 could be expressed as a homodimer and its associated with the activating adaptor protein FcεRIγ. This association allowed efficient phagocytosis of antibody-coated beads. Additionally, cross-linking of DCAR1 on the surface of rat eosinophils lead to production of reactive oxygen species. These data show that DCAR1 is an activating receptor. Its expression on M2 macrophages and eosinophils suggests that it may play a role in the immune response to parasites.

• Jendresen, Charlotte Bille; Daws, Michael Rory & Nilsson, Lars (2018). An improved CPRG colorimetric ligand-receptor signal transduction assay based on beta-galactosidase activity in mammalian BWZ-reporter cells. Journal of pharmacological and toxicological methods.  ISSN 1056-8719.  90, s 67- 75 . doi: 10.1016/j.vascn.2017.11.004 Fulltekst i vitenarkiv.
• Jendresen, Charlotte Bille; Årskog, Vibeke Helen; Daws, Michael Rory & Nilsson, Lars (2017). The Alzheimer's disease risk factors apolipoprotein E and TREM2 are linked in a receptor signaling pathway. Journal of Neuroinflammation.  ISSN 1742-2094.  14:59, s 1- 13 . doi: 10.1186/s12974-017-0835-4
• Thiruchelvam-Kyle, Lavanya; Hoelsbrekken, Sigurd Erik; Sæther, Per Christian; Bjørnsen, Elisabeth Gyllensten; Pende, Daniela; Fossum, Sigbjørn; Daws, Michael Rory & Dissen, Erik (2017). The Activating Human NK Cell Receptor KIR2DS2 Recognizes a β2-Microglobulin–Independent Ligand on Cancer Cells. Journal of Immunology.  ISSN 0022-1767.  198(7), s 2556- 2567 . doi: 10.4049/jimmunol.1600930
• Lobato Pascual, Ana; Sæther, Per Christian; Dahle, Maria Krudtaa; Gaustad, Peter; Dissen, Erik; Fossum, Sigbjørn & Daws, Michael Rory (2013). Rat Macrophage C-type Lectin is an Activating Receptor Expressed by Phagocytic Cells. PLOS ONE.  ISSN 1932-6203.  8(2) . doi: 10.1371/journal.pone.0057406
• Lobato Pascual, Ana; Sæther, Per Christian; Fossum, Sigbjørn; Dissen, Erik & Daws, Michael Rory (2013). Mincle, the receptor for mycobacterial cord factor, forms a functional receptor complex with MCL and FcεRI-γ. European Journal of Immunology.  ISSN 0014-2980.  43(12), s 3167- 3174 . doi: 10.1002/eji.201343752
• Daws, Michael Rory; Dai, Kezheng; Zinöcker, Severin; Naper, Christian; Kveberg, Lise; Hedrich, Hans J; Rolstad, Bent & Vaage, John Torgils (2012). Identification of an MHC Class I Ligand for the Single Member of a Killer Cell Lectin-like Receptor Family, KLRH1. Journal of Immunology.  ISSN 0022-1767.  189(11), s 5178- 5184 . doi: 10.4049/jimmunol.1201983 Vis sammendrag

  Natural killer cells are able to recognize and kill target cells according to differences in MHC class I expression. In rodents, the Ly49 receptors are primarily responsible for this MHC differentiation. We previously described the cloning of a novel C-type lectin–like receptor, KLRH1, encoded in the NK complex adjacent to the Ly49 genes and expressed by subsets of NK and NKT cells. MHC influence on selection of KLRH1+ NK cells in congenic strains suggested that KLRH1 may have an MHC ligand, although we were unable to identify any such ligand. In this study, we have used a sensitive reporter system and Fc fusion protein to demonstrate that KLRH1 binds specifically to the classical MHC class I molecule RT1-A2 of the RT1n haplotype. Cytolytic activity of KLRH1-transfected RNK-16 cells was also inhibited by target cells expressing RT1-A2n. Thus, KLRH1 represents a novel family of MHC allele–specific inhibitory receptors expressed by NK cells.

• Fossum, Sigbjørn; Sæther, Per Christian; Vaage, John Torgils; Daws, Michael Rory & Dissen, Erik (2011). Paired opposing leukocyte receptors recognizing rapidly evolving ligands are subject to homogenization of their ligand binding domains. Immunogenetics.  ISSN 0093-7711.  63(12), s 809- 820 . doi: 10.1007/s00251-011-0553-5
• Shegarfi, Hamid; Dai, Kezheng; Daws, Michael Rory; Ryan, James C.; Vaage, John Torgils; Rolstad, Bent & Naper, Christian (2011). The rat NK cell receptors Ly49s4 and Ly49i4 recognize nonclassical MHC-I molecules on Listeria monocytogenes-infected macrophages. Journal of Leukocyte Biology.  ISSN 0741-5400.  89(4), s 617- 623 . doi: 10.1189/jlb.1010593
• Flornes, Line Mari; Nylenna, Øyvind; Sæther, Per Christian; Daws, Michael Rory; Dissen, Erik & Fossum, Sigbjørn (2010). The complete inventory of receptors encoded by the rat natural killer cell gene complex. Immunogenetics.  ISSN 0093-7711.  62(8), s 521- 530 . doi: 10.1007/s00251-010-0455-y
• Kveberg, Lise; Dai, Kezheng; Westgaard, Ingunn Hagen; Daws, Michael Rory; Fossum, Sigbjørn; Naper, Christian & Vaage, John Torgils (2009). Two major groups of rat NKR-P1 receptors can be distinguished based on chromosomal localization, phylogenetic analysis and Clr ligand binding. European Journal of Immunology.  ISSN 0014-2980.  39(2), s 541- 551 . doi: 10.1002/eji.200838891
• Humphrey, MB; Daws, Michael Rory; Spusta, SC; Niemi, EC; Torchia, JA; Lanier, LL; Seaman, WE & Nakamura, MC (2006). TREM2, a DAP12-associated receptor, regulates osteoclast differentiation and function. Journal of Bone and Mineral Research.  ISSN 0884-0431.  21, s 237- 245
• Chen, TT; Li, L; Chung, DH; Allen, CDC; Torti, SV; Torti, FM; Cyster, JG; Chen, C; Brodsky, FM; Niemi, EC; Nakamura, MC; Seaman, WE & Daws, Michael Rory (2005). TIM-2 is expressed on B-cells and in liver and kidney, and is a receptor for H-ferritin endocytosis. Journal of Experimental Medicine.  ISSN 0022-1007.  202, s 955- 965
• Humphrey, MB; Ogasawara, K; Yao, W; Spusta, SC; Daws, Michael Rory; Lane, NE; Lanier, LL & Nakamura, MC (2004). The signaling adapter protein DAP12 regulates multinucleation during osteoclast development. Journal of Bone and Mineral Research.  ISSN 0884-0431.  19, s 224- 234
• Chung, DH; Humphrey, MB; Nakamura, MC; Seaman, WE & Daws, Michael Rory (2003). CMRF-35-like molecule-1, a novel mouse myeloid receptor, can inhibit osteoclast formation. Journal of Immunology.  ISSN 0022-1767.  171, s 6541- 6548
• Daws, Michael Rory; Sullam, PM; Niemi, EC; Chen, TT & Seaman, WE (2003). Pattern recognition by TREM-2: binding of anionic ligands. Journal of Immunology.  ISSN 0022-1767.  171, s 594- 599
• Chung, DH; Seaman, WE & Daws, Michael Rory (2002). Characterization of TREM-3, an activating receptor on mouse macrophages: definition of a family of single Ig domain receptors on mouse chromosome 17. European Journal of Immunology.  ISSN 0014-2980.  32, s 59- 66
• O'Connell, D; Becerril, B; Roy-Burman, A; Daws, Michael Rory & Marks, JD (2002). Phage versus phagemid libraries for generation of human monoclonal antibodies. Journal of Molecular Biology.  ISSN 0022-2836.  321, s 49- 56
• Daws, Michael Rory; Lanier, LL; Seaman, WE & Ryan, JC (2001). Cloning and characterization of a novel mouse myeloid DAP12-associated receptor family. European Journal of Immunology.  ISSN 0014-2980.  31, s 783- 791
• Karnbach, Claudia; Daws, Michael Rory; Niemi, EC & Nakamura, MC (2001). Immune rejection of a large sarcoma following cyclophosphamide and IL-12 treatment requires both NK and NK T cells and is associated with the induction of a novel NK T cell population. Journal of Immunology.  ISSN 0022-1767.  167, s 2569- 2576
• Ryan, JC; Naper, Christian; Hayashi, Shigenari & Daws, Michael Rory (2001). Physiologic functions of activating natural killer (NK) complex-encoded receptors on NK cells. Immunological Reviews.  ISSN 0105-2896.  181, s 126- 137
• Daws, Michael Rory; Eriksson, Mikael; Öberg, Linda; Ullén, Anders & Sentman, Charles L (1999). H-2Dd engagement of Ly49A leads directly to Ly49A phosphorylation and recruitment of SHP1. Immunology.  ISSN 0019-2805.  97, s 656- 664
• Cilio, CM; Daws, Michael Rory; Malashicheva, A; Sentman, Charles L & Holmberg, D (1998). Cytotoxic T lymphocyte antigen 4 is induced in the thymus upon in vivo activation and its blockade prevents anti-CD3-mediated depletion of thymocytes. Journal of Experimental Medicine.  ISSN 0022-1007.  188, s 1239- 1246
• Westley, BR; Clayton, SJ; Daws, Michael Rory; Molloy, CA & May, FE (1998). Interactions between the oestrogen and insulin-like growth factor signalling pathways in the control of breast epithelial cell proliferation. Biochemical Society Symposium.  ISSN 0067-8694.  63, s 35- 44
• Fahlén, Linda; Khoo, NK; Daws, Michael Rory & Sentman, Charles L (1997). Location-specific regulation of transgenic Ly49A receptors by major histocompatibility complex class I molecules. European Journal of Immunology.  ISSN 0014-2980.  27, s 2057- 2065
• Daws, Michael Rory; Westley, BR & May, FE (1996). Paradoxical effects of overexpression of the type I insulin-like growth factor (IGF) receptor on the responsiveness of human breast cancer cells to IGFs and estradiol. Endocrinology.  ISSN 0013-7227.  137, s 1177- 1186

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• Kristensen, Petter; Levy, Finn; Grahnstedt, Svein G; Martinsen, Aud; Schiel, Anja Elisabeth; Flornes, Line Mari; Daws, Michael Rory; Dissen, Erik & Fossum, Sigbjørn (2011). Oils and Health. Report to the Ministry of Health and Care Services.
• Dahle, Maria Krudtaa & Daws, Michael Rory (2010). Regulation of activating CD300-receptors in human macrophage differentiation and inflammatory activation.
• Lobato Pascual, Ana; Sæther, Per Christian; Fossum, Sigbjørn & Daws, Michael Rory (2010). Exploring expression and function of the rat Macrophage C-type Lectin, Clecsf8. Vis sammendrag

  Innate immune response receptors play an important role in recognizing molecular patterns in pathogens and altered host cells. Among these are the C-type lectin-like receptors, which have been shown to recognize both carbohydrate structures as well as specific protein ligands. The Antigen Presenting cell LEctin-like receptor Complex, APLEC, is an evolutionary conserved gene cluster in the rat, mouse and human, which has been previously described as an immune response locus that influences autoimmunity. This gene complex has been linked to oil-induced arthritis in the rat, and an association has also been shown to rheumatoid arthritis in the man. The Macrophage C-type Lectin, Clecsf8, is a receptor encoded by APLEC. Preliminary data from our group has shown that MCL is upregulated in the arthritis susceptible DA strain, but not in the DA rats containing the arthritis-resistant PVG APLEC genes. We have developed in-house monoclonal antibodies against rat-Clecsf8 to examine the distribution and expression pattern of this receptor in a variety of organs. We have found that this protein is mainly expressed in the monocyte/macrophage lineage, neutrophils and dendritic cells. The presence of Clecsf8 in neutrophils and professional antigen presenting cells suggests a role of this receptor in the early stages of antigen recognition and a possible link to the initiation of the adaptive immunity response.

• Kveberg, Lise; Westgaard, Ingunn Hagen; Dai, Kezheng; Daws, Michael Rory; Fossum, Sigbjørn; Naper, Christian & Vaage, John Torgils (2007). The NKR-P1 family of receptors in rat recognizes C-type lectin related molecules.
• Kveberg, Lise; Westgaard, Ingunn Hagen; Dai, Kezheng; Daws, Michael Rory; Fossum, Sigbjørn; Naper, Christian & Vaage, John Torgils (2007). The NKR-P1 family of receptors in rat recognizes C-type lectin-related molecules.
• Zinöcker, Severin; Dai, Kezheng; Naper, Christian; Daws, Michael Rory; Rolstad, Bent & Vaage, John Torgils (2007). A novel reporter system to identify NK receptor-MHC ligand interactions.

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