Adipose Tissue-Derived Mesenchymal Stem Cells Induce Expansion of Interleukin-10-Producing Regulatory B Cells and Ameliorate Autoimmunity in a Murine Model of Systemic Lupus Erythematosus

作者：Park Min Jung; Kwok Seung Ki; Lee Sung Hee; Kim Eun Kyung; Park Sung Hwan; Cho Mi La^*

来源：Cell Transplantation, 2015, 24(11): 2367-2377.

DOI：10.3727/096368914X685645

• Mesenchymal stem cells (MSCs)
• Regulatory B cells (Bregs)
• Systemic lupus erythematosus (SLE)
• Follicular helper T cells (Tfh cells)
• Interleukin (IL)-10

Mesenchymal stem cells (MSCs) are multipotent cells characterized by immunomodulatory properties and are therefore considered a promising tool for the treatment of autoimmune diseases. One functional B-cell subset, regulatory B cells (Bregs), has recently been shown to restrain excessive inflammatory responses in autoimmune diseases. In the present study, we investigated the impact of human adipose-derived MSCs on Bregs and their therapeutic effect in an animal model of systemic lupus erythematosus (SLE). Coculture of human adipose-derived MSCs with splenocytes from C57BL16 mice expanded the population of interleukin-10-producing B cells (B10 B cells). In vivo treatment with human adipose-derived MSCs reduced serum anti-double-stranded antibody levels and improved renal pathology of lupus mice (Roquin(san/san) mice). MSCs decreased ICOS(+)CD44(+) follicular helper T cells, Th1 cells and Th17 cells, in spleens of Roquin(san/san) mice. In contrast, MSCs increased Foxp3-expressing regulatory T cells. MSCs also decreased the size and number of germinal centers and effector B cells. As expected, in vivo treatment with MSCs expanded the population of Bregs in spleens of Roquin(san/san) mice. Our results indicate that human adipose-derived MSCs induce the expansion of Bregs and ameliorate autoimmunity in a murine model of SLE. These findings suggest that human adipose-derived MSCs may be a promising therapeutic strategy targeting B-cell-mediated autoimmune diseases such as SLE.

• 出版日期2015
• 单位河北医科大学