title: 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.
abstract: 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.
authors.affiliation: The Rheumatism Research Center, The Catholic University of Korea, Seoul, South Korea.
authors.forename: Min-Jung
authors.initials: MJ
authors.lastname: Park
authors.forename: Seung-Ki
authors.initials: SK
authors.lastname: Kwok
authors.forename: Sung-Hee
authors.initials: SH
authors.lastname: Lee
authors.forename: Eun-Kyung
authors.initials: EK
authors.lastname: Kim
authors.forename: Sung-Hwan
authors.initials: SH
authors.lastname: Park
authors.forename: Mi-La
authors.initials: ML
authors.lastname: Cho
mesh_terms: D000273:Adipose Tissue / Q000166:cytology*; D000818:Animals; D060151:B-Lymphocytes, Regulatory / Q000276:immunology*; D004195:Disease Models, Animal; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006801:Humans; D016753:Interleukin-10 / Q000378:metabolism*; D008180:Lupus Erythematosus, Systemic / Q000503:physiopathology / Q000628:therapy*; D045164:Mesenchymal Stem Cell Transplantation; D051379:Mice; D008810:Mice, Inbred C57BL; D013154:Spleen / Q000166:cytology; D013601:T-Lymphocytes / Q000276:immunology; D044767:Ubiquitin-Protein Ligases / Q000235:genetics
chemical_list: D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; C556062:IL10 protein, mouse; D016753:Interleukin-10; C501406:Rc3h1 protein, mouse; D044767:Ubiquitin-Protein Ligases