정민이
2016-10-14T01:06:15Z
2016-10-14T01:06:15Z
2015-04
CELL TRANSPLANTATION, Page. 0-0
0963-6897
1555-3892
http://www.ingentaconnect.com/content/cog/ct/2016/00000025/00000001/art00001
http://hdl.handle.net/20.500.11754/23803
Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the production of autoantibodies to components of the cell nucleus. These autoantibodies are predominantly produced with the help of follicular helper T (Tfh) cells and form immune complexes that trigger widespread inflammatory damage, including nephritis. In recent studies, mesenchymal stem cells (MSCs) elicited diverse, even opposing, effects in experimental and clinical SLE. Here we investigated the effect of human bone marrow-derived MSCs (hBM-MSCs) in a murine model of SLE, the F1 hybrid between New Zealand Black and New Zealand White strains (NZB/W). We found that infusion of female NZB/W mice with hBM-MSCs attenuated glomerulonephritis; it also decreased levels of autoantibodies and the incidence of proteinuria and improved survival. These effects coincided with a decrease in Tfh cells and downstream components. Infiltration of long-lived plasma cells into the inflamed kidney was also reduced in the hBM-MSC-treated mice. Importantly, hBM-MSCs directly suppressed the in vitro differentiation of naive CD4(+) T cells toward Tfh cells in a contact-dependent manner. These results suggest that MSCs attenuate lupus nephritis by suppressing the development of Tfh cells and the subsequent activation of humoral immune components. They thus reveal a novel mechanism by which MSCs regulate humoral autoimmune diseases such as SLE.
We thank Dr. H. S. Kim and I. Y Chang for providing technical assistance and Dr. Julian Gross for editorial assistance. This work was supported by grants of the Korean Health Technology R&D Project, Ministry of Health & Welfare, Korea (HI13C0016 and A120404). The authors declare no conflicts of interest.
en
COGNIZANT COMMUNICATION CORP
Mesenchymal stem cells
MSCs
Follicular helper T (Tfh) cells
Systemic lupus erythematosus
SLE
Autoimmunity
Nephritis
Infusion of human bone marrow-derived mesenchymal stem cells alleviates autoimmune nephritis in a lupus model by suppressing follicular helper T cell development
Article
10.3727/096368915X688173
0-0
CELL TRANSPLANTATION
Jang, Eunkyeong
Jeong, Mini
Kim, Sukhyung
Jang, Kiseok
Kang, Bo-Kyeong
Lee, Dong Yun
Bae, Sang-Cheol
Kim, Kyung Suk
Youn, Jeehee
2015001645
S
RESEARCH INSTITUTE[S]
INSTITUTE OF MEDICAL SCIENCE
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