The expression of TAM receptors and their ligand Gas6 is downregulated in psoriasis

Psoriasis, a common chronic skin disease is, among others, characterized by epidermal hyperplasia and altered cytokine milieu. The most widely held model of psoriasis pathogenesis proposes that keratinocyte hyperproliferation is triggered by cutaneous lymphocyte infiltration, activation and differentiation of inflammatory cells and that these events generate a localized cytokine environment [ ]. Despite the heterogeneity of cytokine networks [ ] these effector molecules both sustain and reinforce the pathogenic cascade in psoriasis. Hence, psoriasis plaques formation involves the interaction between inflammatory and resident tissue cells, primarily mediated by various cytokines such as TNF-α, IL-6, IL-23, IL-17, CXCL8 [ ]. Recently introduced therapeutic approaches in the management of psoriasis indeed depend on neutralizing the given cytokine [ ] which reiterates the central role of secreted effector molecules in the pathophysiology of the disease. These data clearly shows, that even though cytokines play essential role during innate immune responses of the host, their expression must be tightly regulated since unrestrained cytokine secretion generates a chronic inflammatory milieu, leading to autoimmune diseases [ ]. Since elevated cytokine levels, even in the absence of microbial superinfection, are a hallmark of psoriasis we hypothesized malfunctions in the negative regulation of innate immune response and clearance of apoptotic cells in diseased skin. TAM family of receptor tyrosine kinases – Tyro3, Axl, Mer – and their common ligand Gas6, among others, play central role in the intrinsic inhibition of the inflammatory response to pathogens and regulate phagocytosis of apoptotic cells [ , ]. Thus, we sought to determine the expression pattern of these regulators of innate immunity and phagocytosis in a mouse model of psoriasis and subsequently in uninvolved and involved skin of psoriatic patients.