ERK1-mediated immunomodulation of mesenchymal stem cells ameliorates inflammatory disorders

Qing Zhang; Xiao Lei; Fang Wang; Xiaoning He; Lu Liu; Yuxia Hou; Yuan Liu; Fang Jin; Chider Chen; Bei Li

doi:10.1016/j.isci.2023.107868

ERK1-mediated immunomodulation of mesenchymal stem cells ameliorates inflammatory disorders

iScience. 2023 Sep 9;26(10):107868. doi: 10.1016/j.isci.2023.107868. eCollection 2023 Oct 20.

Authors

Qing Zhang^{1

2

3}, Xiao Lei^{1

3}, Fang Wang⁴, Xiaoning He¹, Lu Liu^{1

3}, Yuxia Hou², Yuan Liu⁵, Fang Jin³, Chider Chen⁶, Bei Li¹

Affiliations

¹ State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration & National Clinical Research Center for Oral Diseases & Shaanxi International Joint Research Center for Oral Diseases, Center for Tissue Engineering, School of Stomatology, the Fourth Military Medical University, Xi'an, Shaanxi 710032, China.
² Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Xi'an Jiaotong University, Xi'an, Shaanxi 710004, China.
³ Shannxi Clinical Research Center for Oral Diseases & Department of Orthodontics, School of Stomatology, the Fourth Military Medical University, Xi'an, Shaanxi 710032, China.
⁴ Department of Blood Purification, General Hospital of Central Theater Command of PLA, 68 Huangpu Road, Wuhan, Hubei 430010, China.
⁵ The Affiliated Northwest Women's and Children's Hospital of Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710061, China.
⁶ Department of Oral and Maxillofacial Surgery and Pharmacology, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

Abstract

Immune system disorders, especially T cell disorders, are important therapeutic targets of mesenchymal stem cells (MSCs) in many autoimmune diseases (ADs). Although extracellular regulated protein kinases (ERKs) play a role in MSC therapy by promoting T cell apoptosis, the mechanism remains unclear. Our findings indicate that ERK1^-/- bone marrow MSCs (BMMSCs), but not ERK2^-/- BMMSCs, failed to promote T cell apoptosis due to incapacity to activate the ETS2/AURKA/NF-κB/Fas/MCP-1 cascade. Moreover, ERK1^-/- BMMSCs were unable to upregulate regulatory T cells and suppress T helper 17 cells. Licochalcone A (LA), which promotes ERK pathway activation, enhanced the therapeutic efficacy of MSC therapy in ulcerative colitis and collagen-induced arthritis mice. Our findings suggest that ERK1, but not ERK2, plays a crucial role in regulating T cells in MSCs. LA-treated MSCs provide a strategy to improve the efficacy of MSC-based treatments for ADs.

Keywords: Cell biology; Immunology; Molecular biology; Stem cells research.

Abstract

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