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

• Published in: Cell transplantation Vol. 24; no. 11; p. 2367
• Main Authors: Park, Min-Jung, Kwok, Seung-Ki, Lee, Sung-Hee, Kim, Eun-Kyung, Park, Sung-Hwan, Cho, Mi-La
• Format: Journal Article
• Language: English
• Published: United States SAGE Publishing 01-11-2015
• Subjects: Adipose Tissue - cytology; Animals; B-Lymphocytes, Regulatory - immunology; Disease Models, Animal; Female; Forkhead Transcription Factors - metabolism; Humans; Interleukin-10 - metabolism; Lupus Erythematosus, Systemic - physiopathology; Lupus Erythematosus, Systemic - therapy; Mesenchymal Stem Cell Transplantation; Mice; Mice, Inbred C57BL; Spleen - cytology; T-Lymphocytes - immunology; Ubiquitin-Protein Ligases - genetics
• ISSN: 0963-6897; 1555-3892
• DOI: 10.3727/096368914x685645

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 C57BL/6 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.