| dc.identifier.uri | http://hdl.handle.net/11401/72539 | |
| dc.identifier.uri | http://hdl.handle.net/1951/55470 | |
| dc.description.sponsorship | This work is sponsored by the Stony Brook University Graduate School in compliance with the requirements for completion of degree. | en_US |
| dc.format | Monograph | |
| dc.format.medium | Electronic Resource | en_US |
| dc.language.iso | en_US | |
| dc.publisher | The Graduate School, Stony Brook University: Stony Brook, NY. | |
| dc.type | Dissertation | |
| dcterms.abstract | Growing 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). | |
| dcterms.available | 2012-05-15T18:04:08Z | |
| dcterms.available | 2015-04-24T14:52:30Z | |
| dcterms.contributor | Ghebrehiwet, Berhane | en_US |
| dcterms.contributor | Kenneth Marcu | en_US |
| dcterms.contributor | Patrick Hearing | en_US |
| dcterms.contributor | Richard Kew | en_US |
| dcterms.contributor | Gerald Thomsen | en_US |
| dcterms.contributor | Wenchao Song | en_US |
| dcterms.creator | Hosszu, Kinga | |
| dcterms.dateAccepted | 2012-05-15T18:04:08Z | |
| dcterms.dateAccepted | 2015-04-24T14:52:30Z | |
| dcterms.dateSubmitted | 2012-05-15T18:04:08Z | |
| dcterms.dateSubmitted | 2015-04-24T14:52:30Z | |
| dcterms.description | Department of Genetics | en_US |
| dcterms.format | Monograph | |
| dcterms.format | Application/PDF | en_US |
| dcterms.identifier | Hosszu_grad.sunysb_0771E_10175.pdf | en_US |
| dcterms.identifier | http://hdl.handle.net/11401/72539 | |
| dcterms.identifier | http://hdl.handle.net/1951/55470 | |
| dcterms.issued | 2010-08-01 | |
| dcterms.language | en_US | |
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| dcterms.publisher | The Graduate School, Stony Brook University: Stony Brook, NY. | |
| dcterms.subject | autoimmunity, C1q, Dendritic cells, immunology, systemic lupus | |
| dcterms.subject | Health Sciences, Immunology | |
| dcterms.title | The Role of C1q in Regulation of Monocyte to Dendritic Cell Differentiation: Implications in Autoimmunity | |
| dcterms.type | Dissertation | |
