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dc.contributor.advisorGhebrehiwet, Berhaneen_US
dc.contributor.authorHosszu, Kingaen_US
dc.contributor.otherDepartment of Geneticsen_US
dc.date.accessioned2012-05-15T18:04:08Z
dc.date.available2012-05-15T18:04:08Z
dc.date.issued1-Aug-10en_US
dc.date.submittedAug-10en_US
dc.identifierHosszu_grad.sunysb_0771E_10175.pdfen_US
dc.identifier.urihttp://hdl.handle.net/1951/55470
dc.description.abstractGrowing evidence shows that the first component of complement, C1q, regulates the growth and function of cells committed to the monocyte-derived dendritic cell (DC) lineage. Because C1q regulates both innate and acquired immune responses, we postulated that C1q modulates the monocyte-DC transition at the earliest stages, i.e. at the interface between innate and acquired immunity. Our results corroborate this hypothesis and show that C1q modulates GM-CSF+IL4 induced DC differentiation, as evidenced by retention of CD14 and reduced expression of DC maturation markers and co-stimulatory molecules. C1q induced the development of at least two immature DC (iDC) subsets (CD14hiCD11chiCD16+/-). Moreover, C1q treatment resulted in significantly increased secretion of IFN-γ and MIP-1α after 24 hours, while the number of cells producing these cytokines did not notably change. C1q treatment significantly enhanced the phagocytic uptake capacity of iDCs on day 3, while it did not change their allogeneic immunostimulatory capacity. Taken together, these data suggest that in the absence of danger signals C1q may help maintain steady state conditions by skewing DC differentiation toward cells with monocyte-macrophage-like characteristics. Further results revealed that freshly isolated peripheral blood monocytes carry C1q on their surface even at day 0, when they have not been exposed to DC growth factors. The binding pattern of a monoclonal antibody specific to the globular heads of C1q (gC1q) indicated that C1q is bound to monocytes and iDCs via its globular heads, presumably through gC1qR, the receptor for the globular heads of C1q. Culturing monocyte-DCs in the presence of a monoclonal antibody recognizing the C1q binding site on gC1qR resulted in the development of cells similar to those with C1q treatment, further indicating that C1q/gC1qR interaction is a requisite of early C1q signaling on these cells. Since C1q is synthesized and secreted predominantly by macrophages and DCs, we predict that a C1q-rich environment allows for specific C1q/C1q receptor interactions that may control the transition from the monocyte state (innate immunity) toward the professional antigen presenting cell state (adaptive immunity).en_US
dc.description.sponsorshipStony Brook University Libraries. SBU Graduate School in Department of Genetics. Lawrence Martin (Dean of Graduate School).en_US
dc.formatElectronic Resourceen_US
dc.language.isoen_USen_US
dc.publisherThe Graduate School, Stony Brook University: Stony Brook, NY.en_US
dc.subject.lcshHealth Sciences, Immunologyen_US
dc.subject.otherautoimmunity, C1q, Dendritic cells, immunology, systemic lupusen_US
dc.titleThe Role of C1q in Regulation of Monocyte to Dendritic Cell Differentiation: Implications in Autoimmunityen_US
dc.typeDissertationen_US
dc.description.advisorAdvisor(s): Berhane Ghebrehiwet. Committee Member(s): Kenneth Marcu; Patrick Hearing; Richard Kew; Gerald Thomsen; Wenchao Songen_US
dc.mimetypeApplication/PDFen_US


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