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Journal of immunology

Journal of immunology

IF: 3.4
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Single-Cell RNA Sequencing Identifies WARS1+ Mesenchymal Stem Cells with Enhanced Immunomodulatory Capacity and Improved Therapeutic Efficacy

Published:1 August 2024 DOI: 10.4049/jimmunol.2300752 PMID: 38856632
Xiangxiao Li,?Fengjiao Zhang,?Libo Sun,?Xiaojie Cai,?Fangzhou Lou,?Yang Sun,?Min Gao,?Zhikai Wang,?Sibei Tang,?Li Fan,?Yue Wu,?Xinping Jin,?Siyu Deng,?Zhenyao Xu,?Xuxu Sun,?Qun Li,?Honglin Wang

Abstract

Psoriasis is a common inflammatory skin disorder with no cure. Mesenchymal stem cells (MSCs) have immunomodulatory properties for psoriasis, but the therapeutic efficacies varied, and the molecular mechanisms were unknown. In this study, we improved the efficacy by enhancing the immunomodulatory effects of umbilical cord-derived MSCs (UC-MSCs). UC-MSCs stimulated by TNF-α and IFN-γ exhibited a better therapeutic effect in a mouse model of psoriasis. Single-cell RNA sequencing revealed that the stimulated UC-MSCs overrepresented a subpopulation expressing high tryptophanyl-tRNA synthetase 1 (WARS1). WARS1-overexpressed UC-MSCs treat psoriasis-like skin inflammation more efficiently than control UC-MSCs by restraining the proinflammatory macrophages. Mechanistically, WARS1 maintained a RhoA-Akt axis and governed the immunomodulatory properties of UC-MSCs. Together, we identify WARS1 as a master regulator of UC-MSCs with enhanced immunomodulatory capacities, which paves the way for the directed modification of UC-MSCs for escalated therapeutic efficacy.

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