骨髓间充质干细胞输注对MRL/lpr狼疮鼠B淋巴细胞CXCR4表达的影响

Abstract
Figure/Table
References (0)
Related Citation (6)

Download: PDF (1715 KB) HTML (1 KB)
Export: BibTeX | EndNote (RIS)

Abstract Objective： To study the effects of bone marrow mesenchymal stem cells （BMMSCs） infusion on plasma C3 and IgG concentrations， and CXCR4 expression of B cells and plasma cells in MRL/lpr lupus mice， and to explore the mechanism of BMMSCs in regulating disease activity of systemic lupus erythematosus. Methods： BMMSCs were isolated from C57BL/6 mice and cultured， and then injected into MRL/lpr lupus mice by tail transfusion. All mice were divided into C57BL/6 group （C57BL/6 mice were not injected ）， MRL/lpr group （MRL/lpr mice were not injected with BMMSCs）， BMMSCs infusion group （MRL/lpr mice were injected with BMMSCs at 12 weeks）， and PBS control group （MRL/ lpr mice were injected with PBS at 12 weeks）.At the end of the 20th week， peripheral blood， bone marrow and spleen of mice were taken for flow cytometry analysis to detect CXCR4 expression in B and plasma cells， and then the plasma of the 4 groups were taken for ELISA to detect IgG and C3 level. The kidney of mice was stained with hematoxylineosin. Results： ① Compared with the C57BL/6 group， the plasma C3 level were decreased and IgG level were significantly increased in the MRL/lpr group（all P<0.01）. Compared with C57BL/6 group， the expression of CXCR4 on B cell surface in MRL/lpr group was significantly decreased in peripheral blood， and was significantly increased in bone marrow and spleen（all P<0.01）. The proportion of CXCR4 on plasma cell surface in bone marrow（P<0.05） and spleen（P<0.01） of MRL/lpr group was significantly higher than that of C57BL/6 mice.② Compared with PBS or MRL/lpr group， the level of C3 in BMMSCs group was significantly increased， while the level of IgG was significantly decreased（all P<0.01）. Compared with the PBS group， the expression of CXCR4 on B cell surface of BMMSCs group was significantly increased in peripheral blood（P<0.01）， and significantly decreased in bone marrow（P<0.01） and spleen（P<0.05）. Compared with the MRL/lpr group， the expression of CXCR4 on B cell surface of bone marrow and spleen was significantly decreased （all P<0.01）.③ Compared with PBS group or MRL/lpr group， the expression of CXCR4 on plasma cell surface in bone marrow and spleen of BMMSCs group was significantly decreased（all P<0.05）.④ Renal HE staining suggested attenuation of renal inflammation in MRL/lpr mice after infusion of BMMSCs. Conclusion： BMMSCs infusion can regulate the expression of CXCR4 on the surface of B and plasma cells and improve the disease activity index of MRL/lpr mice.

Received: 28 January 2021

	Service

	E-mail this article
	Add to my bookshelf
	Add to citation manager
	E-mail Alert
	RSS
	Articles by authors
	MA Cui
	TANG Yu
	CHENG Mengwei
	SHI Wei
	ZHENG Wenjuan
	QIU Yingying
	RUI Jinbing
	WANG Yanru

Cite this article:

MA Cui,TANG Yu,CHENG Mengwei等.

Effects of bone marrow mesenchymal stem cells infusion on CXCR4 expression in B cells of MRL/lpr lupus mice

[J]. Journal of Jiangsu University(Medicine Edition), 2021, 31(05): 406-411.

URL:

http://zzs.ujs.edu.cn/xbyxb/EN/ OR http://zzs.ujs.edu.cn/xbyxb/EN/Y2021/V31/I05/406

［1］Signorini V， Elefante E， Zucchi D， et al. One year in review 2020： systemic lupus erythematosus［J］. Clin Exp Rheumatol， 2020，38（4）：592-601.

［2］Ma K， Du W， Wang X， et al. Multiple functions of B cells in the pathogenesis of systemic lupus erythematosus［J］. Int J Mol Sci， 2019，20（23）：6021.

［3］Chong BF， Mohan C. Targeting the CXCR4/CXCL12 axis in systemic lupus erythematosus［J］. Expert Opin Ther Targets， 2009，13（10）：1147-1153.

［4］Hanaoka H， Okazaki Y， Hashiguchi A， et al. Overexpression of CXCR4 on circulating B cells in patients with active systemic lupus erythematosus［J］. Clin Exp Rheumatol， 2015，33（6）：863-870.

［5］Li H， Tian Y， Xie L， et al. Mesenchymal stem cells in allergic diseases： Current status［J］. Allergol Int， 2020，69（1）：35-45.

［6］Cheng RJ， Xiong AJ， Li YH， et al. Mesenchymal stem cells： allogeneic MSC may be immunosuppressive but autologous MSC are dysfunctional in lupus patients［J］.Front Cell Dev Biol， 2019，7：285.

［7］Wang M， Yuan Q， Xie L. Mesenchymal stem cellbased immunomodulation： properties and clinical application［J］.Stem Cells Int， 2018，2018：1-12.

［8］Yuan L， Xiao ZT， Huang XZ， et al. Human embryonic mesenchymal stem cells alleviate pathologic changes of MRL/Lpr mice by regulating Th7 cell differentiation［J］. Ren Fail， 2016，38（9）：1432-1440.

［9］白静.免疫球蛋白与补体C3、C4联合检测对系统性红斑狼疮的诊断价值［J］.医疗装备， 2020，33（4）：32-33.

［10］Flynn RJ. CD95 and the MRLlpr mouse model［J］. Methods Mol Biol， 2017，1557：219-228.

［11］Thong B， Olsen NJ. Systemic lupus erythematosus diagnosis and management［J］. Rheumatology（Oxford）， 2017， 56（suppl_1）：i3-i13.

［12］束庆，范晴晴，刘蕴星，等.间充质干细胞移植在治疗自身免疫性疾病中的应用进展［J］.药学进展， 2019，43（4）：276-281.

［13］Ji J， Wu Y， Meng Y， et al. JAKSTAT signaling mediates the senescence of bone marrowmesenchymal stem cells from systemic lupus erythematosus patients［J］. Acta Biochim Biophys Sin （Shanghai）， 2017，49（3）：1-8.

［14］de la Varga Martínez R，RodríguezBayona B，Aez GA， et al. Clinical relevance of circulating antiENA and antidsDNA secreting cells from SLE patients and their dependence on STAT3 activation［J］. Eur J Immunol， 2017，47（7）：1211-1219.

［15］Malkiel S， Barlev AN， AtishaFregoso Y， et al. Plasma cell differentiation pathways in systemic lupus erythematosus［J］.Front Immunol， 2018，9：427-448.

［16］Ma K， Li J， Wang X， et al.TLR4+CXCR4+ plasma cells drive nephritis development in systemic lupus erythematosus［J］.Ann Rheum Dis， 2018，77（10）：1498-1506.

［17］Adriano T， Laleh K， Caroline V， et al. Longlived plasma cells are early and constantly generated in New Zealand Black/New Zealand White F1 mice and their therapeutic depletion requires a combined targeting of autoreactive plasma cells and their precursors［J］.Arthritis Res Ther， 2015，17（1）：1-12.

［18］Ellyard JI， Avery DT， Mackay CR， et al. Contribution of stromal cells to the migration， function and retention of plasma cells in human spleen： potential roles of CXCL12， IL6 and CD54［J］.Eur J Immunol， 2005，35（3）：699-708.

［19］Wang W， RangelMoreno J， Owen T， et al. Longterm B cell depletion in murine lupus eliminates autoantibodysecreting cells and is associated with alterations in the kidney plasma cell niche［J］.J Immunol， 2014，192（7）：3011-3020.