Role Of RIG-I Antiviral Signaling In The Pathogenesis Of Psoriasis

Psoriasis is a chronic relapsing autoimmune skin disease.The pathogenesis of psoriasis is largely unknow.Recent years,some reports suggest that the etiology of psoriasis is closely related to viral infection,but the molecular mechanism involved is still unclear.Retinoic acid inducible-gene I(RIG-I)has been identified in 2012 as a susceptibility gene in psoriasis.It functions as one of the major cytoplasma sensors of RNA viruses.Here,we show that the activation of RIG-I by 5’ppp-dsRNA,its synthetic ligand,directly causes the production of IL-23 and triggers psoriasis-like skin disease in mice.Repeated injections of IL-23 to the ears failed to induce mouse model of psoriasis in either germ-free or RIG-I deficient mice.Furthermore,RIG-I is significantly upregulated in both the lesional skin of psoriasis patients and IL-23induced mouse model of psoriasis and the upregulation was mainly confined to the CD11c~+dendritic cells(DCs).IL-23 also activates nuclear factor-kappa B(NF-?B)signaling pathway which is downstream of RIG-I to induce IL-23p19 transcription in an auto-regulatory feedback loop.RIG-I serves as both a target and a regulator of IL-23 and clinical improvement in psoriasis with specific targeting of IL-23 has been observed.Thus,our findings uncover a novel RIG-I antiviral signaling pathway for triggering psoriasis and suggest a new hypotheses about the etiology of psoriasis for the first time.Moreover,our research revises the current understanding of psoriasis pathogenesis and proposes a new prevention and therapeutic strategy for psoriasis.