Gene expression profiling to understand the alterations in the monocyte compartment of pediatric systemic lupus erythematosus.

dc.contributor.advisorPascual, Virginia.
dc.contributor.advisorBanchereau, Jacques.
dc.contributor.authorPatel, Pinakeen Shankarbhai.
dc.contributor.departmentBiomedical Studies.en
dc.contributor.otherBaylor University. Institute of Biomedical Studies.en
dc.date.accessioned2008-06-11T17:41:33Z
dc.date.available2008-06-11T17:41:33Z
dc.date.copyright2008-05
dc.date.issued2008-06-11T17:41:33Z
dc.descriptionIncludes bibliographical references (p. 360-379).en
dc.description.abstractBlood monocytes from SLE patients display DC function, as they are able to induce the proliferation of allogeneic T cells. Furthermore, sera from SLE patients induce healthy monocytes to differentiate into DCs. This DC-inducing property is in part due to the presence of type-I IFNs in SLE sera, as well as other, yet uncharacterized factors. To understand these alterations, we performed a thorough phenotypic analysis and gene expression profiling of monocytes from children with active, newly diagnosed and untreated disease. Phenotypic analysis of freshly isolated SLE blood monocytes revealed a modest expansion of CD14highCD16+ cells and an otherwise lack of expression of molecules related to DC function. Further characterization of a fraction of SLE monocytes inducing allogeneic T cell proliferation revealed that upon contact with T cells, SLE monocytes secrete proinflammatory cytokines such as IL-1 and IL-6 and do upregulate expression of innate immunity receptors involved in DC differentiation and molecules responsible for antigen presentation. To recapitulate the initial events leading to monocyte differentiation in this disease, we studied the effects of SLE serum on healthy monocyte at the trasncriptional and protein levels. These studies revealed the upregulation of expression on these cells of chemokine receptor such as CX3CR1 and CCR7, which may lead to the migration of blood monocytes to inflammed tissues and/or secondary lymphoid organs respectively in vivo. There, contact with T cells would lead to the acquisition of antigen presenting function and skewing from tolerogenic to immunogenic responses.en
dc.description.degreePh.D.en
dc.description.statementofresponsibilityby Pinakeen Shankarbhai Patel.en
dc.format.extentxiv, 379 p. : ill.en
dc.format.extent302731 bytes
dc.format.extent3900596 bytes
dc.format.mimetypeapplication/pdf
dc.format.mimetypeapplication/pdf
dc.identifier.urihttp://hdl.handle.net/2104/5190
dc.language.isoen_USen
dc.rightsBaylor University theses are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission. Contact librarywebmaster@baylor.edu for inquiries about permission.en
dc.rights.accessrightsWorldwide access.en
dc.rights.accessrightsAccess changed 5/24/11.
dc.subjectSystemic lupus erythematosus -- Pathophysiology.en
dc.subjectMonocyte.en
dc.subjectDendritic cells.en
dc.subjectGene expression.en
dc.titleGene expression profiling to understand the alterations in the monocyte compartment of pediatric systemic lupus erythematosus.en
dc.typeThesisen

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