Olfactory Ecto-mesenchymal Stem Cell-derived Exosomes Ameliorate Murine Sjögren's Syndrome Via Suppressing Tfh Cell Response

Overview

Journal Rheumatol Immunol Res

Specialty Allergy & Immunology

Date 2023 Mar 7

PMID 36879843

Authors

Ke Rui

Ziwei Shen

Na Peng

Futao Zhao

Yuan Tang

Shiyi Liu

Xinyi Xu

Chang Liu

Ling Wu

Jie Tian

Liwei Lu

Affiliations

Soon will be listed here.

Abstract

Objectives: To investigate the effect of olfactory ecto-mesenchymal stem cell-derived exosomes (OE-MSC-Exos) on T follicular helper (Tfh) cell response and their implication in treating experimental Sjögrens syndrome (ESS).

Methods: C57BL/6 mice were immunized with salivary glands (SG) proteins to induce ESS mouse model. OE-MSC-Exos were added to the Tfh cell polarization condition, and the proportion of Tfh cells was detected by FCM. The PD-L1 of OE-MSCs was silenced with small interfering RNA to extract siPD-L1-OE-MSC-Exos.

Results: We found that transfer of OE-MSC-Exos markedly attenuated disease progression and reduced Tfh cell response in mice with ESS. In culture, OE-MSC-Exos potently inhibited the differentiation of Tfh cells from naïve T cells. Moreover, OE-MSC-Exos expressed high level of the ligand for the programmed cell death protein 1 (PD-L1), knocking down PD-L1 expression in OE-MSC-Exos significantly decreased their capacity to suppress Tfh cell differentiation in vitro. Consistently, transfer of OE-MSC-Exos with PD-L1 knockdown exhibited profoundly diminished therapeutic effect in ESS mice, accompanied with sustained Tfh cell response and high levels of autoantibody production.

Conclusion: Our results suggest that OE-MSC-Exos may exert their therapeutic effect in ameliorating ESS progression via suppressing Tfh cell response in a PD-L1-dependent manner.

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