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dc.contributor.advisorGomer, Richard H
dc.creatorCox, Nehemiah
dc.date.accessioned2017-08-21T14:28:38Z
dc.date.available2017-08-21T14:28:38Z
dc.date.created2015-05
dc.date.issued2015-05-04
dc.date.submittedMay 2015
dc.identifier.urihttp://hdl.handle.net/1969.1/161252
dc.description.abstractFibrosis is caused by scar tissue formation in internal organs and is associated with 45% of deaths in the U.S. Pentraxins are a group of evolutionarily conserved proteins that have profound effects of the innate immune system and regulate the development of fibrosis. The pentraxin Serum Amyloid P (SAP) alleviates fibrosis in mice and two human clinical trials, whereas C-reactive protein (CRP) which resembles SAP exacerbates fibrosis. Surprisingly, these two pentraxins bind the same Fcγ receptors (FcγR) with similar affinities but have opposite effects. In this dissertation, I elucidate the role of FcγR in the regulation of the innate immune system by pentraxins. I find that although FcγR play a role in the regulation of immune cells by SAP, they are not necessary for SAP effects. SAP mainly uses the C-type lectin receptor DC-SIGN to alter immune responses and through its interaction with DC-SIGN SAP differentiates itself from CRP. I also found that a polycyclic aminothiazole DC-SIGN ligand and anti-DC-SIGN antibodies mimic the effects of SAP in vitro. In mice, the aminothiazole alleviates acute lung inflammation and pulmonary fibrosis. The aminothiazole alleviates pulmonary fibrosis by upregulating the anti-inflammatory cytokine IL-10 in lung epithelial cells. Together, these results suggest that SAP activates DC-SIGN to regulate the innate immune system differently from CRP, and that the aminothiazole and anti-DC-SIGN antibodies are potential therapeutics for fibrosis.en
dc.format.mimetypeapplication/pdf
dc.language.isoen
dc.subjectInnate immune systemen
dc.subjectFibrosisen
dc.subjectPentraxinsen
dc.subjectDC-SIGNen
dc.subjectSerum Amyloid Pen
dc.titleRegulation of Innate Immune Responses and Fibrosis by Serum Amyloid Pen
dc.typeThesisen
thesis.degree.departmentBiologyen
thesis.degree.disciplineBiologyen
thesis.degree.grantorTexas A & M Universityen
thesis.degree.nameDoctor of Philosophyen
thesis.degree.levelDoctoralen
dc.contributor.committeeMemberBarondeau, David P
dc.contributor.committeeMemberHu, James C
dc.contributor.committeeMemberLockless, Steve W
dc.type.materialtexten
dc.date.updated2017-08-21T14:28:38Z
local.etdauthor.orcid0000-0002-2369-4741


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