{"@context":"http://iiif.io/api/presentation/2/context.json","@id":"https://repo.library.stonybrook.edu/cantaloupe/iiif/2/manifest.json","@type":"sc:Manifest","label":"The Role of C1q in Regulation of Monocyte to Dendritic Cell Differentiation: Implications in Autoimmunity","metadata":[{"label":"dc.description.sponsorship","value":"This work is sponsored by the Stony Brook University Graduate School in compliance with the requirements for completion of degree."},{"label":"dc.format","value":"Monograph"},{"label":"dc.format.medium","value":"Electronic Resource"},{"label":"dc.identifier.uri","value":"http://hdl.handle.net/11401/72539"},{"label":"dc.language.iso","value":"en_US"},{"label":"dc.publisher","value":"The Graduate School, Stony Brook University: Stony Brook, NY."},{"label":"dcterms.abstract","value":"Growing evidence shows that the first component of complement, C1q, regulates the\ngrowth and function of cells committed to the monocyte-derived dendritic cell (DC)\nlineage. Because C1q regulates both innate and acquired immune responses, we\npostulated that C1q modulates the monocyte-DC transition at the earliest stages, i.e. at the\ninterface between innate and acquired immunity. Our results corroborate this hypothesis\nand show that C1q modulates GM-CSF+IL4 induced DC differentiation, as evidenced by\nretention of CD14 and reduced expression of DC maturation markers and co-stimulatory\nmolecules. C1q induced the development of at least two immature DC (iDC) subsets\n(CD14hiCD11chiCD16+/-). Moreover, C1q treatment resulted in significantly increased\nsecretion of IFN-\u03b3 and MIP-1\u03b1 after 24 hours, while the number of cells producing these\ncytokines did not notably change. C1q treatment significantly enhanced the phagocytic\nuptake capacity of iDCs on day 3, while it did not change their allogeneic \nimmunostimulatory capacity. Taken together, these data suggest that in the absence of\ndanger signals C1q may help maintain steady state conditions by skewing DC\ndifferentiation toward cells with monocyte-macrophage-like characteristics.\nFurther results revealed that freshly isolated peripheral blood monocytes carry\nC1q on their surface even at day 0, when they have not been exposed to DC growth\nfactors. The binding pattern of a monoclonal antibody specific to the globular heads of\nC1q (gC1q) indicated that C1q is bound to monocytes and iDCs via its globular heads,\npresumably through gC1qR, the receptor for the globular heads of C1q. Culturing\nmonocyte-DCs in the presence of a monoclonal antibody recognizing the C1q binding\nsite on gC1qR resulted in the development of cells similar to those with C1q treatment,\nfurther indicating that C1q/gC1qR interaction is a requisite of early C1q signaling on\nthese cells. Since C1q is synthesized and secreted predominantly by macrophages and\nDCs, we predict that a C1q-rich environment allows for specific C1q/C1q receptor\ninteractions that may control the transition from the monocyte state (innate immunity)\ntoward the professional antigen presenting cell state (adaptive immunity)."},{"label":"dcterms.available","value":"2015-04-24T14:52:30Z"},{"label":"dcterms.contributor","value":"Kenneth Marcu"},{"label":"dcterms.creator","value":"Hosszu, Kinga"},{"label":"dcterms.dateAccepted","value":"2015-04-24T14:52:30Z"},{"label":"dcterms.dateSubmitted","value":"2015-04-24T14:52:30Z"},{"label":"dcterms.description","value":"Department of Genetics"},{"label":"dcterms.format","value":"Application/PDF"},{"label":"dcterms.identifier","value":"http://hdl.handle.net/11401/72539"},{"label":"dcterms.issued","value":"2010-08-01"},{"label":"dcterms.language","value":"en_US"},{"label":"dcterms.provenance","value":"Made available in DSpace on 2015-04-24T14:52:30Z (GMT). No. of bitstreams: 3\nHosszu_grad.sunysb_0771E_10175.pdf.jpg: 1894 bytes, checksum: a6009c46e6ec8251b348085684cba80d (MD5)\nHosszu_grad.sunysb_0771E_10175.pdf.txt: 174791 bytes, checksum: 99591460f5e26f68ec8a5da5374654d8 (MD5)\nHosszu_grad.sunysb_0771E_10175.pdf: 1448375 bytes, checksum: e3637a26d9b927b013ef563d3e9c0cb5 (MD5)\n  Previous issue date:    1"},{"label":"dcterms.publisher","value":"The Graduate School, Stony Brook University: Stony Brook, NY."},{"label":"dcterms.subject","value":"Health Sciences, Immunology"},{"label":"dcterms.title","value":"The Role of C1q in Regulation of Monocyte to Dendritic Cell Differentiation: Implications in Autoimmunity"},{"label":"dcterms.type","value":"Dissertation"},{"label":"dc.type","value":"Dissertation"}],"description":"This manifest was generated dynamically","viewingDirection":"left-to-right","sequences":[{"@type":"sc:Sequence","canvases":[{"@id":"https://repo.library.stonybrook.edu/cantaloupe/iiif/2/canvas/page-1.json","@type":"sc:Canvas","label":"Page 1","height":1650,"width":1275,"images":[{"@type":"oa:Annotation","motivation":"sc:painting","resource":{"@id":"https://repo.library.stonybrook.edu/cantaloupe/iiif/2/13%2F01%2F25%2F130125092197553752917413174695227072690/full/full/0/default.jpg","@type":"dctypes:Image","format":"image/jpeg","height":1650,"width":1275,"service":{"@context":"http://iiif.io/api/image/2/context.json","@id":"https://repo.library.stonybrook.edu/cantaloupe/iiif/2/13%2F01%2F25%2F130125092197553752917413174695227072690","profile":"http://iiif.io/api/image/2/level2.json"}},"on":"https://repo.library.stonybrook.edu/cantaloupe/iiif/2/canvas/page-1.json"}]}]}]}