| First Author | Németh T | Year | 2017 |
| Journal | J Invest Dermatol | Volume | 137 |
| Issue | 10 | Pages | 2131-2139 |
| PubMed ID | 28576735 | Mgi Jnum | J:248994 |
| Mgi Id | MGI:6094456 | Doi | 10.1016/j.jid.2017.05.017 |
| Citation | Nemeth T, et al. (2017) The Syk Tyrosine Kinase Is Required for Skin Inflammation in an In Vivo Mouse Model of Epidermolysis Bullosa Acquisita. J Invest Dermatol 137(10):2131-2139 |
| abstractText | 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 leukotriene B4 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 leukotriene B4 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. |
