Abstract
BackgroundEvidence has shown that psoriasis is closely associated with infection; however, the mechanism of this association remains unclear. In mammalian cells, viral or bacterial infection is accompanied by the release of cytosolic DNA, which in turn triggers the production of type-I interferons (IFNs). Type I IFNs and their associated genes are significantly upregulated in psoriatic lesions. RIG-I is also highly upregulated in psoriatic lesions and is responsible for IFN production. However, RIG-I mediated regulatory signaling in psoriasis is poorly understood.MethodsWe screened a cDNA library and identified potential RIG-I interacting partners that may play a role in psoriasis.ResultsWe found that serine/arginine-rich splicing factor 1 (SRSF1) could specifically interact with RIG-I to facilitate RIG-I mediated production of type-I IFN that is triggered by cytosolic DNA. We found SRSF1 associates with RNA polymerase III and RIG-I in a DNA-dependent manner. In addition, treatment with a TNFα inhibitor downregulated SRSF1 expression in peripheral blood mononuclear cells (PBMCs) from psoriasis vulgaris patients.DiscussionBased on the abundance of pathogenic cytosolic DNA that is detected in psoriatic lesions, our finding that RIG-I interacts with SRSF1 to regulate type-I IFN production reveals a critical link regarding how cytosolic DNA specifically activates aberrant IFN expression. These data may provide new therapeutic targets for the treatment of psoriasis.
Highlights
Psoriasis is a chronic inflammatory skin disease that is currently recognized as a complex immune disorder involving both innate and adaptive immune regulation [1,2]
We found that serine/arginine-rich splicing factor 1 (SRSF1) could interact with RIG-I to facilitate RIG-I mediated production of type-I IFN that is triggered by cytosolic DNA
Based on the abundance of pathogenic cytosolic DNA that is detected in psoriatic lesions, our finding that RIG-I interacts with SRSF1 to regulate type-I IFN production reveals a PLOS ONE | DOI:10.1371/journal.pone
Summary
Evidence has shown that psoriasis is closely associated with infection; the mechanism of this association remains unclear. Viral or bacterial infection is accompanied by the release of cytosolic DNA, which in turn triggers the production of type-I interferons (IFNs). Type I IFNs and their associated genes are significantly upregulated in psoriatic lesions. RIG-I is highly upregulated in psoriatic lesions and is responsible for IFN production. RIG-I mediated regulatory signaling in psoriasis is poorly understood. Data Availability Statement: All relevant data are within the paper and its Supporting Information files.
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