Keratinocyte exosomal LOC285194 ameliorates psoriasis by inhibiting the differentiation of CD4+T cells to Th17 cells through regulating miR-211-5p/SIRT1 axis

Keratinocytes exosome participates in the pathogenesis of psoriasis and exosomes always carry long non-coding RNAs (lncRNAs) into target cells to function as an essential immune regulator in psoriasis-related diseases. LncRNA LOC285194 is closely associated with the occurrence of psoriasis. However, whether keratinocyte exosomal LOC285194 participates in the process of psoriasis remains vague. Exosomes were authenticated by transmission electron microscope and nanoparticle tracking analysis (NTA). Relative gene expression was determined by reverse transcription-polymerase chain reaction (RT-PCR). Flow cytometry was used to monitor the proportion of immune cells. Fluorescence in situ hybridization was employed to determine the colocalization of lncRNA and miRNA. Keratinocyte exosomal LOC285194 was reduced in psoriasis patients and had a negative association with Th17 cell infiltration in psoriasis patients. LOC285194-downregulation contributed to the differentiation of CD4⁺T cells to Th17 cells. Cytokine cocktail treatment reduced LOC285194 expression in keratinocytes and keratinocyte exosome, subsequently promoted the differentiation of CD4⁺T cells to Th17 cells and Th17 cells-related molecular levels including IL-17A, IL-22 and TNF-α, which were notably abrogated by LOC285194-upregulation in keratinocytes. As a sponge of LOC285194, miR-211-5p inhibition induced the increase of Th17 cell proportion in CD4⁺T cells, while exosomes treatment isolated from cytokine cocktail-exposed keratinocytes further enhanced Th17 cell proportion, which were abolished by LOC285194 overexpressed-exosome treatment. Furthermore, silent information regulator 1 (SIRT1) mediated the regulation role of miR-211-5p on Th17 cell production. Combined with the imiquimod-induced psoriasis animal model, exosomes isolated from LOC285194-overexpressing keratinocytes relieved psoriasis symptom through regulating miR-211-5p/SIRT1 axis. LOC285194 upregulation in keratinocytes promoted the keratinocyte exosomal LOC285194, that could be absorbed by CD4⁺T cells, leading to the inhibition of Th17 cell differentiation through targeting miR-211-5p/SIRT1 axis. This study provides a novel molecular mechanism of Th17 cell accumulation-mediated psoriasis.