Possible Roles of IL-27 in the Pathogenesis of Psoriasis

Abstract

The immunological significance of IL-27 has been reported and discussed in various Th1/Th17-mediated inflammatory diseases. However, its importance in psoriasis is unknown. We investigated pathophysiological roles of IL-27 in psoriasis in this study. Serum IL-27 levels in psoriatic patients were significantly higher than those in healthy controls, and correlated with disease severity and serum IFN-gamma levels. An immunohistochemical analysis revealed the infiltration of IL-27-secreting cells in the papillary dermis of psoriatic skin lesions but not in skin lesions with atopic dermatitis or normal skin. Furthermore, IL-27 alone greatly induced in vitro CXCL9, CXCL10, and CXCL11 production and tyrosine phosphorylation of signal transducer and activator of transcription 1 in normal human keratinocytes, while it suppressed the tumor necrosis factor-alpha-induced production of IL-1alpha and CCL20. These results indicate that IL-27 may promote the onset of psoriasis, while it may simultaneously attenuate the expanded inflammation in this disease. Our results implicate potential therapeutic effects of IL-27 for psoriasis.

Psoriasis in humans is associated with down‐regulation of galectins in dendritic cells

“…We found higher IL-27 mRNA expression in lesional skin of psoriasis patients than in skin samples from healthy donors (Supplemental Fig. 1), according to previous data [19]. IL-27 expression was also above in asymptomatic skin from psoriasis patients, but this difference was not statistically significant.…”

The IL-18 Antagonist IL-18–Binding Protein Is Produced in the Human Ovarian Cancer Microenvironment

“…However, the precise contribution of IL-27 to immune response, inflammation, and cancer is still poorly understood. On one hand, IL-27 has proinflammatory effects through the induction of CXCL10 in macrophages in inflammatory skin disorders (43). However, IL-27 may limit the proinflammatory and immune-enhancing activities of IL-18 in the skin through IL-18BP induction (33) and may dampen autoimmunity, as Il27 À/À mice were more susceptible to experimental autoimmune encephalomyelitis (44).…”

Human Primary Keratinocytes Show Restricted Ability to Up-regulate Suppressor of Cytokine Signaling (SOCS)3 Protein Compared with Autologous Macrophages

“…Furthermore, IL-27 promotes a proinflammatory type 1 response by priming human primary keratinocytes, macrophages or inflammatory dendritic epidermal cells for IL-6, TNF␣, CXCL10, and IL-23 production, respectively. IL-27 is therefore significantly involved in initiating and driving the chronic phase of inflammatory skin diseases (1)(2)(3)7). Interestingly, as shown by Owaki et al (9) for CD4 ϩ T cells, the STAT3-responsive molecule SOCS3 3 is also induced by IL-27.…”

“…Recently, we reported that IL-27 was found to be expressed in the chronic (Th1-dominated) but not in the acute phase of eczema (Th2-dominated) (2). In addition, Shibata et al (1) found an infiltration of IL-27-secreting cells in psoriatic skin lesions. In both cases it may act as a strong proinflammatory mediator able to maintain Th1 cell response in the epidermal compartment.…”