dc.contributor.author |
Németh, Tamás |
|
dc.contributor.author |
Virtic, O |
|
dc.contributor.author |
Sitaru, C |
|
dc.contributor.author |
Mócsai, Attila |
|
dc.date.accessioned |
2018-03-13T09:42:17Z |
|
dc.date.available |
2018-03-13T09:42:17Z |
|
dc.date.issued |
2017 |
|
dc.identifier.citation |
pagination=2131-2139;
journalVolume=137;
journalIssueNumber=10;
journalTitle=JOURNAL OF INVESTIGATIVE DERMATOLOGY; |
|
dc.identifier.uri |
http://repo.lib.semmelweis.hu//handle/123456789/4509 |
|
dc.identifier.uri |
doi:10.1016/j.jid.2017.05.017 |
|
dc.description.abstract |
The inflammatory form of epidermolysis bullosa acquisita is caused by autoantibodies against type VII collagen (C7), a component of the dermal-epidermal junction. We have previously shown that myeloid Src-family kinases mediate skin inflammation triggered by anti-C7 antibodies. Here we identify the Syk tyrosine kinase as a critical component of autoantibody-induced skin inflammation downstream of Src-family kinases. Immobilized C7-anti-C7 immune complexes triggered neutrophil activation and Syk phosphorylation in a Src-family kinase-dependent manner. Bone marrow chimeric mice lacking Syk in their hematopoietic compartment were completely protected from skin inflammation triggered by anti-C7 antibodies despite normal circulating anti-C7 levels. Syk deficiency abrogated the accumulation of CXCL2, IL-1beta and LTB4 at the site of inflammation and resulted in defective in vivo neutrophil recruitment. Syk-/- neutrophils had a normal intrinsic migratory capacity but failed to release CXCL2 or LTB4 upon activation by immobilized C7-anti-C7 immune complexes, indicating a role for Syk in the amplification of the inflammation process. These results identify Syk as a critical component of skin inflammation in a mouse model of epidermolysis bullosa acquisita and as a potential therapeutic target in epidermolysis bullosa acquisita and other mechanistically related inflammatory skin diseases such as bullous pemphigoid. |
|
dc.relation.ispartof |
urn:issn:0022-202X |
|
dc.title |
The Syk tyrosine kinase is required for skin inflammation in an in vivo mouse model of epidermolysis bullosa acquisita |
|
dc.type |
Journal Article |
|
dc.date.updated |
2017-09-22T10:49:26Z |
|
dc.language.rfc3066 |
en |
|
dc.identifier.mtmt |
3269267 |
|
dc.identifier.wos |
000411210000091 |
|
dc.identifier.scopus |
85031023152 |
|
dc.identifier.pubmed |
28576735 |
|
dc.contributor.department |
SE/AOK/I/Élettani Intézet |
|
dc.contributor.department |
SE/AOK/I/ÉI/MTA-SE Lendület Gyulladásélettani Kutatócsoport |
|
dc.contributor.institution |
Semmelweis Egyetem |
|
dc.mtmt.swordnote |
FELTÖLTŐ: Sonnevend Kinga - sonnevend.kinga@med.semmelweis-univ.hu
FELTÖLTÉSI MEGJEGYZÉS: A cikk elkészültét az MTA Bolyai János Kutatási Ösztöndíj támogatta. |
|
dc.mtmt.swordnote |
Tamás Németh and Oana Virtic authors contributed equally to this work. |
|