The effect of plasma exosomal microRNA- 148a- 3p on the CD4+ T cell function and its mechanism in the pathogenesis of psoriasis

Abstract

Psoriasis represents a chronic inflammatory skin disease occurring globally. We investigated the role of plasma exosomal microRNA (miR)- 148a- 3p and its target gene Bim in psoriasis. Plasma exosomes (Exos) and CD4⁺ T cells were extracted from psoriatic patients. miR- 148a- 3p expression in Exos and CD4⁺ T cells of psoriatic patients, the proportions of CD4⁺ T cell subsets, and the contents of anti-inflammatory/pro-inflammatory factors were determined by RT-qPCR, flow cytometry and ELISA. The correlation between plasma exosomal miR- 148a- 3p and CD4⁺ T cell subsets in psoriatic patients was analyzed by Pearson’s analysis. The psoriatic mouse was treated with Exos/antagomir miR- 148a- 3p. Histopathological changes in the skin were observed. The CD4⁺ T cell subset levels, serum cytokine contents and miR- 148a- 3p expression in the blood were measured. The miR- 148a- 3p-Bim targeted binding relationship was predicted and verified by Starbase database and dual-luciferase assay. The Bim expression in psoriatic mice was determined. Psoriatic patients had highly-expressed miR- 148a- 3p in both Exos and CD4⁺ T cells, and abnormal CD4⁺ T cell subsets and cytokine levels. Plasma exosomal miR- 148a- 3p was correlated with the CD4⁺ T cell subsets in psoriatic patients. Exos caused down-regulated miR- 148a- 3p level in skin tissues of mouse, regulated CD4⁺ T cell function and aggravated the symptoms in psoriatic mice. miR- 148a- 3p repression partially reversed the role of Exos in CD4⁺ T cell function and psoriasis-like symptoms. Exos-carried miR- 148a- 3p targeted Bim in CD4⁺ T cells of psoriatic mice. Plasma exosomal miR- 148a- 3p targeted Bim to affect the dysfunction of CD4⁺ T cells in psoriatic mice, thereby aggravating the psoriasis-like symptoms.