Increased Expression of Toll-Like Receptor 4 in Skin of Dogs with Discoid Lupus Erythematous (DLE)

SIMPLE SUMMARY: Discoid lupus erythematous (DLE) is a common autoimmune skin disorder of dogs. The aim of this study was to evaluate the expression of TLR4, a bacterial lipopolysaccharide sensor, in skin of dogs with DLE and in normal skin to evaluate a possible involvement of this receptor in the disease pathogenesis. Skin samples of affected dogs had a diffuse and intense expression of TLR4, both in the epidermis and in inflammatory infiltrates. The expression was higher in DLE skin compared to normal skin. The high TLR4 expression might play an important pathogenic role in the ongoing immunopathologic process. ABSTRACT: Discoid lupus erythematous (DLE) is a common autoimmune skin disorder of dogs where keratinocytes play a pivotal role both in the innate and adaptive immune responses. As for the innate response, pattern recognition receptors (PRR), including Toll-like receptors (TLRs), can activate macrophages and immune tissue cells allowing for transmission and transduction of signals through cytokine and chemokine release to improve host defenses. In particular, TLR4 can also recognize endogenous molecules such as heat shock proteins produced during reactions to tissue damage. The aim of this study was to evaluate the expression of TLR4, a bacterial lipopolysaccharide sensor, in the skin of dogs with DLE and in normal skin to evaluate a possible involvement of this receptor in the disease pathogenesis. Skin samples of affected dogs had a diffuse and intense expression of TLR4 in the epidermis. Also, the inflammatory infiltrates were immunolabelled. The expression was significantly higher in DLE skin compared to normal skin (**** p < 0.0001). In conclusion, dogs with DLE showed an altered expression of TLR4, which might play an important pathogenic role in the ongoing immunopathologic process, thus being considered a valuable therapeutic potential target for DLE.