title: Allogenic mesenchymal stem cell transplantation ameliorates nephritis in lupus mice via inhibition of B-cell activation.
abstract: Recent evidence indicates that bone marrow-derived mesenchymal stem cells (BM-MSCs) possess immunosuppressive properties both in vitro and in vivo. We have previously demonstrated that transplantation of human MSCs can significantly improve the autoimmune conditions in MRL/lpr mice. The current study aimed to determine the mechanisms by which murine BM-MSC transplantation (MSCT) ameliorates nephritis in MRL/lpr mice. In this study, we found that MSCT can significantly prolong the survival of MRL/lpr mice. Eight weeks after transplantation, MSCT-treated mice showed significantly smaller spleens than control animals, with fewer marginal zones (MZs), T1, T2, activated B-cells, and plasma cells. Moreover, serum levels of B-cell activating factor (BAFF) and IL-10 in MSCT-treated mice decreased significantly compared to those in the control group, while levels of serum TGF-β were increased. Notably, decreased BAFF expression in both spleen and kidney was accompanied by decreased production of anti-dsDNA autoantibodies and proteinuria in MSCT-treated mice. Since BAFF is mainly expressed by T-cells and dendritic cells, we incubated BM-MSCs and DCs together and found that the production of BAFF by DCs was suppressed by MSCs. Thus, our findings suggest that MSCT may suppress the excessive activation of B-cells via inhibition of BAFF production in MRL/lpr mice.
authors.affiliation: Department of Immunology and Rheumatology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China.
authors.forename: Xiaolei
authors.initials: X
authors.lastname: Ma
authors.forename: Nan
authors.initials: N
authors.lastname: Che
authors.forename: Zhifeng
authors.initials: Z
authors.lastname: Gu
authors.forename: Jing
authors.initials: J
authors.lastname: Huang
authors.forename: Dandan
authors.initials: D
authors.lastname: Wang
authors.forename: Jun
authors.initials: J
authors.lastname: Liang
authors.forename: Yayi
authors.initials: Y
authors.lastname: Hou
authors.forename: Gary
authors.initials: G
authors.lastname: Gilkeson
authors.forename: Liwei
authors.initials: L
authors.lastname: Lu
authors.forename: Lingyun
authors.initials: L
authors.lastname: Sun
mesh_terms: D000818:Animals; D001323:Autoantibodies / Q000276:immunology / Q000378:metabolism; D053264:B-Cell Activating Factor / Q000097:blood; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology; D002478:Cells, Cultured; D005260:Female; D016753:Interleukin-10 / Q000097:blood; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D008213:Lymphocyte Activation; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D051379:Mice; D008807:Mice, Inbred BALB C; D019463:Mice, Inbred MRL lpr; D009393:Nephritis / Q000378:metabolism / Q000473:pathology / Q000601:surgery / Q000628:therapy*; D011507:Proteinuria / Q000175:diagnosis; D013154:Spleen / Q000378:metabolism / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000097:blood; D014184:Transplantation, Homologous
chemical_list: D001323:Autoantibodies; D053264:B-Cell Activating Factor; D016212:Transforming Growth Factor beta; D016753:Interleukin-10