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Mesenchymal stem cells-derived extracellular vesicles ameliorate lupus nephritis by regulating T and B cell responses

Authors :
Cuifang Li
Feifeng Wu
Jueyi Mao
Yang Wang
Junquan Zhu
Kimsor Hong
Haotian Xie
Xin Zhou
Jidong Tian
Chuan Wen
Source :
Stem Cell Research & Therapy, Vol 15, Iss 1, Pp 1-12 (2024)
Publication Year :
2024
Publisher :
BMC, 2024.

Abstract

Abstract Background Human umbilical cord mesenchymal stem cells-derived extracellular vesicles (hUCMSC-EVs) have potent immunomodulatory properties similar to parent cells. This study investigated the therapeutic effects and immunomodulatory mechanisms of hUCMSC-EVs in an experimental lupus nephritis model. Methods The hUCMSC-EVs were isolated by using differential ultracentrifugation. In vivo, the therapeutic effects of hUCMSC-EVs in lupus-prone MRL/lpr mice were investigated, and the mechanisms of treatment were explored according to the abnormal T and B cell responses among both the spleen and kidney. Results MRL/lpr mice treated with hUCMSC-EVs reduced proteinuria extent, serum creatinine and renal pathological damage; decreased splenic index and serum anti-dsDNA IgG level; and improved survival rate. hUCMSC-EVs lowered the percentage of T helper (Th)1 cells, double-negative T (DNT) cells, and plasma cells among splenocytes; inhibited the infiltration of Th17 cells but promoted regulatory T (Treg) cells in the kidney, followed by a reduction in pro-inflammatory cytokine levels(IFN-γ, IL-2, IL-6, IL-21, and IL-17 A). In addition, hUCMSC-EVs inhibited the activation of STAT3 and down-regulated IL-17 A protein levels in the kidney. Conclusion The results of this study demonstrated that hUCMSC-EVs had therapeutic effects on experimental lupus nephritis (LN) by regulating Th1/Th17/Treg imbalance and inhibiting DNT and plasma cells. Additionally, hUCMSC-EVs inhibited Th17 cell differentiation in kidney by regulating the IL-6/STAT3/IL-17 signal pathway, which might be an important mechanism for alleviating renal injury. Taken together, we demonstrated that hUCMSC-EVs regulating T and B cell immune responses might represent a novel mechanism of hUCMSCs in treating LN, thus providing a new strategy for treating LN.

Details

Language :
English
ISSN :
17576512
Volume :
15
Issue :
1
Database :
Directory of Open Access Journals
Journal :
Stem Cell Research & Therapy
Publication Type :
Academic Journal
Accession number :
edsdoj.fff780a687884b3db3e971e2aa85923e
Document Type :
article
Full Text :
https://doi.org/10.1186/s13287-024-03834-w