dc.contributor.author
Hazzan, Tarek
dc.contributor.author
Eberle, Jürgen
dc.contributor.author
Worm, Margitta
dc.contributor.author
Babina, Magda
dc.date.accessioned
2019-12-13T11:15:45Z
dc.date.available
2019-12-13T11:15:45Z
dc.identifier.uri
https://refubium.fu-berlin.de/handle/fub188/26237
dc.identifier.uri
http://dx.doi.org/10.17169/refubium-25997
dc.description.abstract
Mast cells (MCs) play critical roles in allergic and inflammatory reactions and contribute to multiple pathologies in the skin, in which they show increased numbers, which frequently correlates with severity. It remains ill-defined how MC accumulation is established by the cutaneous microenvironment, in part because research on human MCs rarely employs MCs matured in the tissue, and extrapolations from other MC subsets have limitations, considering the high level of MC heterogeneity. Thymic stromal lymphopoietin (TSLP)-released by epithelial cells, like keratinocytes, following disturbed homeostasis and inflammation-has attracted much attention, but its impact on skin MCs remains undefined, despite the vast expression of the TSLP receptor by these cells. Using several methods, each detecting a distinct component of the apoptotic process (membrane alterations, DNA degradation, and caspase-3 activity), our study pinpoints TSLP as a novel survival factor of dermal MCs. TSLP confers apoptosis resistance via concomitant activation of the TSLP/ signal transducer and activator of transcription (STAT)-5 / myeloid cell leukemia (Mcl)-1 route and a newly uncovered TSLP/ c-Jun-N-terminal kinase (JNK)/ B-cell lymphoma (Bcl)-xL axis, as evidenced by RNA interference and pharmacological inhibition. Our findings highlight the potential contribution of TSLP to the MC supportive niche of the skin and, vice versa, highlight MCs as crucial responders to TSLP in the context of TSLP-driven disorders.
en
dc.rights.uri
https://creativecommons.org/licenses/by/4.0/
dc.subject
RNA interference
en
dc.subject.ddc
600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit::610 Medizin und Gesundheit
dc.title
Thymic Stromal Lymphopoietin Interferes with the Apoptosis of Human Skin Mast Cells by a Dual Strategy Involving STAT5/Mcl-1 and JNK/Bcl-xL
dc.type
Wissenschaftlicher Artikel
dcterms.bibliographicCitation.articlenumber
829
dcterms.bibliographicCitation.doi
10.3390/cells8080829
dcterms.bibliographicCitation.journaltitle
Cells
dcterms.bibliographicCitation.originalpublishername
MDPI AG
dcterms.bibliographicCitation.volume
8
refubium.affiliation
Charité - Universitätsmedizin Berlin
refubium.resourceType.isindependentpub
no
dcterms.accessRights.openaire
open access
dcterms.bibliographicCitation.pmid
31387206
dcterms.isPartOf.eissn
2073-4409