REAL

The Syk tyrosine kinase is required for skin inflammation in an in vivo mouse model of epidermolysis bullosa acquisita

Németh, Tamás and Virtic, Oana and Sitaru, Cassian and Mócsai, Attila (2017) The Syk tyrosine kinase is required for skin inflammation in an in vivo mouse model of epidermolysis bullosa acquisita. JOURNAL OF INVESTIGATIVE DERMATOLOGY, 137 (10). pp. 2131-2139. ISSN 0022-202X

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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.

Item Type: Article
Subjects: R Medicine / orvostudomány > RL Dermatology / bőrgyógyászat
SWORD Depositor: MTMT SWORD
Depositing User: MTMT SWORD
Date Deposited: 22 Sep 2017 11:25
Last Modified: 22 Sep 2017 11:25
URI: http://real.mtak.hu/id/eprint/63453

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