Original Article
Umbilical cord mesenchymal stem cell modulates immune cell subsets in lupus mice
Saisai Huang, Dandan Wang, Wei Deng, Zhuoya Zhang, Weiwei Chen, Wei Kong, Genhong Yao, Lingyun Sun
Published 2016-01-15
Cite as Chin J Rheumatol, 2016, 20(1): 4-插页1-1. DOI: 10.3760/cma.j.issn.1007-7480.2016.01.002
Abstract
ObjectiveThe purpose of this study is to observe the changes of immune cell subsets in lupus mice after umbilical cord mesenchymal stem cells (UC-MSCs) transplantation.
MethodsB6.MRL-Faslpr lupus mice were randomly divided into the following three groups: the UC-MSCs treated group, the fibroblast like synoviocytes (FLS) treated group and the untreated group. MSC (1×106) or FLS (1×106) were injected into the tail vein of lupus mice respectively. Four weeks after treatment, the spleen index was calculated. The pathological changes of kidney were assessed by HE staining. The frequencies of immune cell subsets in spleen and macrophage in kidney as well as abdominal cavity were analyzed by flow cytometry. Data were analyzed with t test.
ResultsThe spleen index of UC-MSCs treated lupus mice [(79±9) mg/10 g] and IgG level [(7.5±1.5) mg/ml] were significantly decreased when compared with FLS treated group [(147±23) mg/10 g, t=2.78, P<0.01] [(17.0±2.8) mg/ml, t=3.00, P<0.01] and the untreated group [(156±16) mg/10 g, t=4.29, P<0.01] [(16.7±1.6) mg/ml, t=4.01, P<0.01]. HE staining also showed that the pathological changes of kidney were alleviated after MSCs transplantation. In addition, the frequency of plasma cells in the untreated group [(2.612±0.318)% vs (0.306±0.017)%, t=7.22, P<0.01] and the FLS treated group [(2.412±0.297)% vs (0.306±0.017)%, t=7.07, P<0.01] were markedly higher than MSCs treatment[(0.306±0.017)%]. Moreover, the frequency of CD25+ Foxp3+/CD4+ Treg in the MSCs treated group[(15.08±0.81)%] was significantly increased compared with the untreated group [(8.02±0.47)%, t=7.45, P<0.01] and FLS treated group [(8.80±0.23)%, t=7.39, P<0.01]. MSCs treatment resulted in a decrease in CXCR5+PD1+/CD4+ Tfh and IFNγ+/CD4+ Th1 subset, compared with the untreated group [(14.3±1.5)% vs (31.5±3.3)%, t=5.25, P<0.01] [(1.78±0.27)% vs (5.93±1.56)%, t=2.60, P<0.05] and the FLS treated group [(14.3±1.5)% vs (28.8±2.2)%, t=5.49, P<0.01] [(1.78±0.27)% vs (4.88±0.81)%, t=3.61, P<0.01]. The frequency of macrophage in kidney of the MSCs treated group[(3.52±0.37)%] was markedly increased compared with the untreated group[(1.58±0.29)%, t=3.25, P<0.01], while neither the IL4+/CD4+ Th2 subset nor the IL17+/CD4+ Th17subset and the frequency of macrophage in abdominal cavity showed significant changes in the three groups.
ConclusionThese findings suggest that the therapeutic effects of MSCs on lupus mice may mediate through increasing the frequency of spleen Treg and renal macrophage and decreasing the frequency of Tfh, Th1 and plasma cells.
Key words:
Mesenchymal stem cells; Lupus erythematosus, systemic; Immune, cellular
Contributor Information
Saisai Huang
Department of Rheumatology and Immunology, the Affiliated Drum Tower Hospital of Nanjing University Medical School, Jiangsu 210008, China
Dandan Wang
Wei Deng
Zhuoya Zhang
Weiwei Chen
Wei Kong
Genhong Yao
Lingyun Sun