Plasma EVs Display Antigen-Presenting Characteristics in Patients With Allergic Rhinitis and Promote Differentiation of Th2 Cells.

Shu-Bin Fang,Qing-Ling Fu,Xiao-Qing Liu,De-Hua Chen,Zhi-Rou Zhou,Dong Chen,Bi-Xin He,Ya-Qi Peng

doi:10.3389/fimmu.2021.710372

Abstract

BackgroundAllergic rhinitis (AR) is characterized by IgE-mediated mucosa response after exposure to allergens. Extracellular vesicles (EVs) are nano-size vesicles containing biological cargos for intercellular communications. However, the role of plasma EVs in pathogenesis of AR remains largely unknown.MethodsPlasma EVs from patients with AR were isolated, quantified, and characterized. The expression of Der p 1 and antigen-presenting molecules on EVs was determined by Western blot, flow cytometry, or ELISA. PKH26- and CFSE (carboxyfluorescein succinimidyl ester)-stained AR-EVs were used to determine the uptake of EVs by CD4+T cells and their effects on CD4+T cell proliferation, respectively.ResultsPlasma EVs in healthy control (HC) and AR patients were similar in the concentration of particles, expression for specific EV markers, and both had structural lipid bilayer. However, the levels of Der p 1 on plasma EVs from both mild and moderate-severe AR patients were significantly higher than that on HC. The levels of antigen-presenting molecules on plasma EVs were similar from three subjects. Moreover, levels of Der p 1 on EVs in plasma, but not nasal secretion, were significantly associated with the symptom score of AR patients and level of plasma IL-13. Additionally, plasma EVs from patients with AR promoted the development of Th2 cells, while no effect was found on CD4+ T-cell proliferation.ConclusionsPlasma EVs derived from patients with AR exhibited antigen-presenting characteristics and promoted differentiation of Th2 cells, thus providing novel understanding of the pathogenesis of AR.

Highlights

Allergic rhinitis (AR) is one of the most common allergic diseases that globally affects 10% to 40% of the population across all age groups [1]
We first isolated plasma Extracellular vesicles (EVs) from healthy control (HC) and AR patients that were sensitive to HDM by differential centrifugation, and we found no significant difference on the concentration of plasma EVs derived from HC, M-AR, and S-AR as determined by NTA (Figure 1A)
EVs isolated from HC and AR patients were both positive in specific EV markers, such as CD9, CD63, CD81, TSG101, and Alix, as determined by Western blot (Figure 1C)

Summary

Introduction

Allergic rhinitis (AR) is one of the most common allergic diseases that globally affects 10% to 40% of the population across all age groups [1]. Extracellular vesicles (EVs) are nano-vesicles that are substantially released by almost all cells and extensively involved in physiological and pathological processes in human bodies [5]. Based on their size and mechanism of formation, these nano-sized particles are generally classified into exosomes released by multivesicular endosomes and microvesicles pinching off from plasma membrane [6]. Previous studies have shown that miRNAs contained in EVs were able to exhibit immunoregulatory effects on allergic airway inflammation [9,10,11]. The role of plasma EVs in pathogenesis of AR remains largely unknown

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Conclusion