Type1 Interferons Potential Initiating Factors Linking Skin Wounds With Psoriasis Pathogenesis

Abstract

Psoriasis is a chronic autoimmune skin disease that can often be triggered upon skin injury, known as Koebner phenomenon. Type 1 interferons (IFNα and IFNβ), 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 IFNβ from KCs and IFNα 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. IFNβ 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.

Psoriasis and Antimicrobial Peptides

“…Type 1 interferons (IFN-α and IFN-β) are key cytokines that activate autoimmunity, such as systemic lupus erythematosus, and are activated in response to viral infection [93]. IFN-α and IFN-β are suggested to play an indispensable role in initiating psoriasis during skin injury [94]. Type I IFN is important for the pathogenesis of psoriasis and activates autoimmune T cells through the differentiation of dendritic cells [94,95].…”

“…IFN-α and IFN-β are suggested to play an indispensable role in initiating psoriasis during skin injury [94]. Type I IFN is important for the pathogenesis of psoriasis and activates autoimmune T cells through the differentiation of dendritic cells [94,95]. Zhang et al showed that, while IFN-α is primarily produced by pDCs in the dermis, IFN-β is predominantly produced by epidermal keratinocytes in skin wounds and psoriasis lesions [69].…”

“…Psoriasis shows the Köbner phenomenon. Inflammation induced by DAMPs released due to microinjuries or scratches, and the enhanced recognition of DAMPs by antimicrobial peptides, may be involved in the mechanism underlying the Köbner phenomenon [94].…”

Psoriatic Dermal-derived Mesenchymal Stem Cells Reduce Keratinocyte Junctions, and Increase Glycolysis

“…Meanwhile, the decreased KC junctions also dysregulated KC differentiation. Finally, the disequilibrium of KC activity leads to psoriasis characterized by epidermal hyperplasia and aberrant differentiation (32).…”

Immunoinflammatory Rheumatic Diseases Associated With Type I Interferon: New Evidence

“…Таким образом, нарушение в системе ИФН типа I является важным компонентом патогенеза ИВРЗ. Кроме того, активация пДК, вызывающая гиперпродукцию ИФН типа I, играет фундаментальную роль в развитии псориаза [119], «парадоксального» псориаза, возникающего на фоне лечения ингибиторами ФНОα [120], а также поражения кожи при СКВ, дискоидной кожной красной волчанке [121] и «лекарственной» волчанке [122]. Ингибиторы JAK эффективны при псориазе и других иммуновоспалительных заболеваниях кожи (атопический дерматит, витилиго, алопеция и др.)…”