Enhanced migration and immunoregulatory capacity of BMSCs mediated by overexpression of CXCR4 and IL-35. (October 2022)

• Record Type: Journal Article
• Authors: Tan, Chen; Tan, Songwei; Zhang, Hao; Zhang, Man; Fan, Heng; Nan, Zhen; Liu, Xingxing; Wang, Wenzhu; Zhang, Lijuan; Deng, Shuangjiao; Zuo, Dongmei; Tang, Qing
• Is Part Of: Molecular immunology. Volume 150(2022)
• Page Start: 1
• Page End: 8
• Publication Date: 2022-10
• Subjects: BMSCs -- IL-35 -- CXCR4 -- Immunoregulation -- Homing; Immunochemistry -- Periodicals; Molecular biology -- Periodicals; Immunochemistry -- Periodicals; Allergy and Immunology -- Periodicals; Molecular Biology -- Periodicals; Immunochimie -- Périodiques; Biologie moléculaire -- Périodiques; Immunochemistry; Molecular biology; Periodicals; Electronic journals; 571.96
• DOI: 10.1016/j.molimm.2022.07.005
• Languages: English
• ISSNs: 0161-5890

Abstract

Abstract: Bone marrow-derived mesenchymal stem cells (BMSCs) have been widely studied for their applications in immunoregulation and tissue repair. However, the therapeutic effects of BMSCs in the body are limited, partly due to the low homing efficiency of BMSCs to affected parts. The stromal cell-derived factor 1 (SDF-1)/C-X-C chemokine receptor type 4 (CXCR4) axis is well known to play an essential role in the homing of BMSCs. Interleukin 35 (IL-35) is a newly discovered cytokine confirmed to inhibit overactivated immune function and have a good therapeutic effect on autoimmune diseases. In this study, we innovatively developed dual gene modification of BMSCs by transducing CXCR4 and IL-35 and found that the migration and immunomodulatory activity of genetically engineered BMSCs were significantly enhanced compared to their natural counterparts. These results suggest that BMSCs modified by dual overexpression of CXCR4 and IL-35 may provide a potential treatment strategy for autoimmune diseases. Graphical Abstract: ga1 Highlights: CXCR4 overexpression promotes migration of BMSCs to SDF-1. CXCR4-dependent homing efficiency due to reduction of E-cadherin and promotion of N-cadherin and vimentin proteins in BMSCs. IL-35 overexpression enhances the immunosuppressive function of BMSCs. Dual CXCR4/IL-35 overexpression promotes BMSCS migration and immunosuppression.