The Role Of Interferon Kappa (IFN-?) In The Pathogenesis Of Psoriasis

ObjectivePsoriasis is a common chronic skin disease associated with skin immune dysregulation.Previous studies reported that type ? interferon(IFN)-IFN?/? play an important role in the pathogenesis of psoriasis.IFN-? is a type ? IFN that specifically expresses in skin keratinocytes.We aim to investigate whether IFN-? expression is aberrant in psoriasis lesions,and if so,whether IFN-? participates in the pathogenesis of psoriasis.Methods Immunohistochemistry staining was used to detect IFN-? protein expression in psoriasis vulgaris lesions,eczema,lichen sclerosis,condyloma acuminatum,lichen planus and normal skin tissues.Image Pro-Plus software was used to semi-quantify the staining positive signals.In vitro primary keratinocyte culture system was used to investigate whether IFN-? regulates keratinocytes differentiation,and whether psoriasis-associated cytokines and pathogen pattern recognition receptor agonists regulates IFN-? gene expression.Finally,we used Imiquimod(IMQ)induced psoriasis murine models to investigate whether IFN-? cytokine or anti-IFN-? antibody can affect psoriasis symptoms.Results 1?IFN-? protein is significantly increased in psoriasis skin lesions(p?0.05),while it is significantly decreased in eczema lesions and lichen sclerosis lesions as compared to normal skin.Its expression has no change in condyloma acuminatum and lichen planus as compared to normal skin 2?IFN-? cannot regulate keratinocytes differentiation;its expression can be induced by IFN-??IFN-??IFN-? and TNF-?,as well as cytosolic nucleic acid sensor agonist PolyI:C and PolydA:dT in both undifferentiated and differentiatied keratinocytes.3?We successful established Imiquimod(IMQ)-induced murine psoriasis model.However,subcutaneous administration of recombinant mouse IFN-? didn't induced psoriasis-like skin lesion although TNF-? and IL-17 A were significantly induced.Subcutaneous administration of IFN-? or anti-IFN-? antibody didn't enhance or reduce IMQ-induced psoriasis symptoms.Conclusion 1?IFN-? protein is significantly increased in psoriatic lesions as compared to other skin diseases and normal skin,suggesting that IFN-? can be a biomarker for psoriasis disease.2?Using siRNA knockdown and addition of recombinant IFN-?,we demonstrate that IFN-? does not regulate keratinocyte differentiation,indicating it doesn't directly involve in dysregulation of epidermis differentiation program in psoriasis.3?The up-regulation of IFN-? may be caused by psoriasis associated cytokine as well as cytosolic nucleic acid sensor induced signaling pathway.4?Subcutaneous administration of recombinant IFN-? didn't induce psoriasis skin lesion.Subtaneous administration of rIFN-? or anti-IFN-? antibody have no effect to IMQinduced psoriasis symptoms,indicating that IFN-? may not involve in the pathogenesis of psoriasis.