Type1 Interferons Potential Initiating Factors Linking Skin Wounds With Psoriasis Pathogenesis

Psoriasis is a chronic autoimmune skin disease that can often be triggered upon skin injury, known as Koebner phenomenon. Type 1 interferons (IFN alpha and IFN beta), key cytokines that activate autoimmunity during viral infection, have been suggested to play an indispensable role in initiating psoriasis during skin injury. Type 1 IFN-inducible gene signature has been identified as one of the major upregulated gene signatures in psoriatic skin. Type 1 IFNs treatments often directly induce or exacerbate psoriasis, whereas blocking type 1 IFNs signaling pathway in animal models effectively inhibits the development of T cell-mediated skin inflammation and psoriasis-like inflammatory diseases. Epidermal keratinocytes (KCs) occupy the outermost position in the skin and are the first responder to skin injury. Skin injury rapidly induces IFN beta from KCs and IFN alpha from dermal plasmacytoid dendritic cells (pDCs) through distinct mechanisms. Host antimicrobial peptide LL37 potentiates double-stranded RNA (dsRNA) immune pathways in keratinocytes and single-stranded RNA or DNA pathways in pDCs, leading to production of distinct type 1 IFN genes. IFN beta from KC promotes dendritic cell maturation and the subsequent T cell proliferation, contributing to autoimmune activation during skin injury and psoriasis pathogenesis. Accumulating evidences have indicated an important role of this dsRNA immune pathway in psoriasis pathogenesis. Together, this review describes how skin injury induces type 1 IFNs from skin cells and how this may initiate autoimmune cascades that trigger psoriasis. Targeting keratinocytes or type 1 IFNs in combination with T cell therapy may result in more sustainable effect to treat auto-inflammatory skin diseases such as psoriasis.