A protein called SYK is a major regulator of the inflammatory response carried out by myeloid cells in mouse models of epidermolysis bullosa acquisita (EBA), showing potential for a new therapeutic target, researchers discovered.
Findings were published in the study, “Whole-Genome Expression Profiling in Skin Reveals SYK As a Key Regulator of Inflammation in Experimental Epidermolysis Bullosa Acquisita,” in the journal Frontiers in Immunology
EBA is caused by the development of autoantibodies — self-attacking antibodies — against an essential skin protein called type VII collagen, which causes significant inflammation and skin blistering.
Therapeutic options are limited for many autoimmune diseases, including EBA, resulting in a high, unmet need for new and effective therapies.
To investigate potential therapeutic targets, researchers analyzed the gene expression profile of an EBA mouse model, compared with healthy mice.
One of the genes identified from this analysis was Sykb (spleen tyrosine kinase, or SYK). SYK protein levels were found to be significantly higher in mice with EBA than in healthy mice, as well as in skin samples from patients with a condition called bullous pemphigoid, which is similar to EBA.
Researchers focused their efforts on SYK, since it has also been considered a potential therapeutic target in other autoimmune diseases.
To validate the importance of SYK in EBA, they tried to induce EBA in mice by administering antibodies against type VII collagen in the presence of a SYK inhibitor called BAY61-3606.
Blocking SYK activity in the presence of the antibodies almost completely stopped the induction of EBA, compared with mice that received the antibodies but no SYK inhibitor.
Furthermore, using mice with a SYK protein deficiency, researchers were able to show that the activity of SYK on myeloid cells, which are responsible for carrying out the inflammatory activity in EBA, is required for the induction of the disease.
Therefore, researchers suggested “SYK expression in myeloid cells as a requirement to promote inflammation in autoantibody-driven pathologies.”
They believe that SYK inhibition can protect the animals from developing EBA, and suggest these results should encourage the use of “SYK and SYK-regulated genes as potential therapeutic targets for EBA, as well as diseases with autoantibody-driven pathology.”