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dc.contributor.advisorThaiss, Friedrich (Prof. Dr.)
dc.contributor.authorChen, Meilan
dc.date.accessioned2020-10-19T13:16:22Z-
dc.date.available2020-10-19T13:16:22Z-
dc.date.issued2016
dc.identifier.urihttps://ediss.sub.uni-hamburg.de/handle/ediss/6989-
dc.description.abstractAccumulative evidences indicated the critical role for CD4+ T cells in the pathogenesis of glomerulonephritis, the molecule(s) involving in regulation of the development and functions of CD4+ T cells to mediate glomerulonephritis is poorly understood. NF-κB transcription family is known as a major regulator of T cells development and functions and participates into multiple inflammation based diseases. However, whether NF-κB functions in CD4+ T cells are critical for glomerulonephritis or not remains unclear. NF-κB is activated by an IκB kinase (IKK) complex comprised of two distinct kinase subunits, IKK1 (IKKα) and IKK2 (IKKβ), plus a regulatory protein, NEMO (IKKγ), which is essential for activation of NF-κB. Here, we specifically deleted IKK2 and/or NEMO in CD4+ T cells to investigate the role of canonical NF-κB pathway in glomerulonephritis. In general, our data showed that knockout of IKK2 and/or NEMO in CD4+ T cells decreased the number of T cells as previously reported under physiological conditions. However, mice with knockout of IKK2 and/or NEMO in CD4+ T cells did not alter the progression of glomerulonephritis showing similar renal functions by examination of albumin-to-creatinine ratio and blood urea nitrogen levels (BUN), and comparable morphology of kidney by quantifying the glomerular/tubulointerstitium damage, and renal crescent levels compared to control mice at 10th day in a well-established nephrotoxic serum nephritis (NTN) induced glomerulonephritis model. We did find an increased infiltration ability of CD3+ and CD4+ T cells into kidney after NTN induction in all types of knockout mice but eventually exhibited similar number of CD3+ T cells and comparable percentage of CD4+ T cells residual in overall renal and glomerular tissues by immunohistochemical and FACS analysis. Interestingly, the infiltration levels for different subtypes of CD4+ T cells were distinct from each other in the injury kidney: more Th1 and Th17 cells and less Treg cells were observed in IKK2 and/or NEMO knockout mice comparing with control mice after NTN induction. However, similar expression levels of proinflammatoy chemokines, including IL-1b, TNF-α, CCL2, CCL5 and CCL20 in all types of knockout mice and control mice, were detected. Consistently, the activation of inflammatory related regulator NF-κB in renal cells was also unaltered by western blotting analysis. Thus, our observations implied that inactivation of NF-κB in CD4+ T cells is not involved in alteration of the severity of NTN induced glomerulonephritis. In addition, to uncover which molecules in CD4+ T cells participate into NTN induced glomerulonephritis, microarray based genome profiling was performed by comparing genes expression in CD4+ T cells from kidney spleen that with or without NTN induction. Thus, to identify novel molecule(s) which are essential/critical for T cells mediated glomerulonephritis greatly benefits to clinic treatment of inflammatory renal diseases.en
dc.language.isoenen
dc.publisherStaats- und Universitätsbibliothek Hamburg Carl von Ossietzky
dc.rightshttp://purl.org/coar/access_right/c_abf2
dc.subjectT-Zellende
dc.subjectNF-κBde
dc.subjectGlomerulonephritisde
dc.subjectMikroarrayde
dc.subjectT cellsen
dc.subjectNF-κBen
dc.subjectGlomerulonephritisen
dc.subjectmicroarrayen
dc.subject.ddc610 Medizin, Gesundheit
dc.titleRole for IKK2- and NEMO-Kinase Mediated Nuclear Factor kappa B (NF-κB) Activation in CD4+ T Lymphocytes in Nephrotoxic Serum Nephritis (NTN) Induced Glomerulonephritis Miceen
dc.title.alternativeRolle bei IKK2- und NEMO-Kinase-vermitteltem Kernfaktor kappa B (NF-κB) Aktivierung in CD4 + T-Lymphozyten bei nephrotoxischer Serumnephritis (NTN) Induzierte Glomerulonephritis Mäusede
dc.typedoctoralThesis
dcterms.dateAccepted2016-11-23
dc.rights.ccNo license
dc.rights.rshttp://rightsstatements.org/vocab/InC/1.0/
dc.subject.bcl44.45 Immunologie
dc.subject.bcl44.61 Innere Medizin
dc.subject.bcl44.88 Urologie, Nephrologie
dc.type.casraiDissertation-
dc.type.dinidoctoralThesis-
dc.type.driverdoctoralThesis-
dc.type.statusinfo:eu-repo/semantics/publishedVersion
dc.type.thesisdoctoralThesis
tuhh.opus.id8233
tuhh.opus.datecreation2016-12-12
tuhh.type.opusDissertation-
thesis.grantor.departmentMedizin
thesis.grantor.placeHamburg
thesis.grantor.universityOrInstitutionUniversität Hamburg
dcterms.DCMITypeText-
tuhh.gvk.ppn876083017
dc.identifier.urnurn:nbn:de:gbv:18-82333
item.advisorGNDThaiss, Friedrich (Prof. Dr.)-
item.grantfulltextopen-
item.languageiso639-1other-
item.fulltextWith Fulltext-
item.creatorOrcidChen, Meilan-
item.creatorGNDChen, Meilan-
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