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AuthorSiebert, Lena Mariadc.contributor.author
Date of accession2016-03-15T09:08:44Zdc.date.accessioned
Available in OPARU since2016-03-15T09:08:44Zdc.date.available
Year of creation2013dc.date.created
AbstractBruton´s tyrosine kinase (Btk) is mainly involved in B cell-receptor signaling and therefore plays a critical role for B cell development and function. Without Btk, B cells arrest in an early pre-B cell state. Mutations in the Btk gene cause XLA (X linked Agammaglobulinemia) in humans and Xid (X linked immunodeficiency) in mice, both mainly characterized by the loss of mature B cells, which leads to a severe immunodeficiency. It became evident that Btk-deficiency also affects the myeloid cell compartment. Especially, antigen presenting dendritic cells (DC) play a critical role for the function of immunity as they initiate appropriate immune responses to pathogens and link innate and adaptive immunity. Therefore, we evaluated the effect of Btk on myeloid DC with emphasis to their development, expression of surface-marker and ability to chemotaxis and T cell stimulation. Bone marrow-derived myeloid DC were generated in the presence of GM-CSF (granulocyte macrophage colony-stimulating factor) and stimulated by the ligands of Toll-like receptor (TLR) TLR3 (Poly I:C),TLR 4 (LPS), TLR7/8 (Imiquimod) and TLR9 (ODN). Our data indicate, that generation-efficiency of bone marrow-derived myeloid DC is impaired without Btk function. Furthermore, Btk-Knockout DC showed potentially reduced expression-levels of MHC-II, CD54 (ICAM 1) and CD184 (CXCR4), but potentially increased expression-levels of CD11a, CD18, CD43, CD44 and CD197 (CCR7). Also chemotactic migration stimulated by the signals of MIP-3 beta und SDF 1 alpha was impaired in Btk-Knockout DC. We further demonstrated that DC might show enhanced stimulation of T cells without Btk-function. Analysis of different TLR-stimulations revealed a role for Btk in MyD88-dependent as well as in MyD88-independent TLR-signaling pathways.dc.description.abstract
Languagededc.language.iso
PublisherUniversität Ulmdc.publisher
LicenseStandarddc.rights
Link to license texthttps://oparu.uni-ulm.de/xmlui/license_v3dc.rights.uri
KeywordAgammaglobulinämiedc.subject
KeywordBTKdc.subject
KeywordXiddc.subject
Dewey Decimal GroupDDC 610 / Medicine & healthdc.subject.ddc
MeSHAgammaglobulinemiadc.subject.mesh
MeSHAmmaglobulinaemia tyrosine kinasedc.subject.mesh
MeSHDendritic cellsdc.subject.mesh
TitleDie Rolle der Bruton-Tyrosinkinase in murinen myeloiden dendritischen Zellendc.title
Resource typeDissertationdc.type
DOIhttp://dx.doi.org/10.18725/OPARU-3028dc.identifier.doi
PPN782352987dc.identifier.ppn
URNhttp://nbn-resolving.de/urn:nbn:de:bsz:289-vts-88320dc.identifier.urn
GNDAntikörpermangelsyndromdc.subject.gnd
GNDDendritische Zelledc.subject.gnd
FacultyMedizinische Fakultätuulm.affiliationGeneral
Date of activation2014-04-01T14:33:40Zuulm.freischaltungVTS
Peer reviewneinuulm.peerReview
Shelfmark print versionW: W-H 13.612uulm.shelfmark
DCMI TypeTextuulm.typeDCMI
VTS ID8832uulm.vtsID
CategoryPublikationenuulm.category
Bibliographyuulmuulm.bibliographie


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