Abstract

Background

Long non-coding RNAs (lncRNAs) have been implicated in the pathogenesis of autoimmune diseases. Our previous research demonstrated that AGAP2-AS1 in keratinocytes is involved in the pathogenesis of psoriasis, but its effect on CD4 + T cell differentiation remains unclear.

Methods

Exosomes were extracted from HaCaT cells using a reagent kit and verified by TEM (Transmission Electron Microscope), NTA (Nanoparticle Tracking Analysis), and Western Blot. We incubated exosomes with CD4 + T cells and detected the distribution of AGAP2-AS1 by fluorescence microscopy. Flow cytometry and ELISA were used to detect CD4 + T cell differentiation. In addition, the relationship between AGAP2-AS1/miR-424-5p/SGK1 and its effect on CD4 + T cell differentiation were confirmed by bioinformatics analysis, dual luciferase reporter gene experiments, quantitative real-time PCR, flow cytometry, and ELISA.

Results

We found that exosomes derived from TNF-α-treated HaCaTs were able to deliver AGAP2-AS1 to CD4 + T cells, promoting Th1 and Th17 differentiation. In CD4 + T cells, AGAP2-AS1 promotes Th1 and Th17 differentiation via the miR-424-5p/SGK1 axis.

Conclusion

Psoriatic HaCaTs deliver AGAP2-AS1 to CD4 + T cells via exosomes, inducing Th1 and Th17 differentiation through the miR-424-5p/SGK1 axis, thereby promoting the progression of psoriasis. These findings provide novel insights into the pathogenesis of psoriasis and potential therapeutic targets.

MeSH

Cells, Genes, Cell Differentiation, Micrornas, Rna, Untranslated, Exosomes, Psoriasis, Rna, Long Noncoding, Rna