title: Human umbilical cord-derived mesenchymal stem cells protect against experimental colitis via CD5(+) B regulatory cells.
abstract: To clarify the effect of human umbilical cord-derived mesenchymal stem cell (hUC-MSCs) treatment on colitis and to explore the role of CD5(+) B cells in MSC therapy.
  
  
  
  The trinitrobenzenesulfonic acid (TNBS)-induced colitis mouse model was used. HUC-MSCs were transferred peritoneally. Survival rates, colitis symptoms, and macroscopic and histologic scores were evaluated. CD4(+) T helper (Th) cell subgroups and CD5(+) regulatory B cell (Bregs) in lymphocytes were quantitated by flow cytometry. Cytokine levels were detected by ELISA and Bio-plex. CD5(+) B cells were isolated for in vitro co-culture and adaptive transfer.
  
  
  
  HUC-MSC treatment alleviated TNBS-induced colitis by increasing survival rates, relieving symptoms, and improving macroscopic and histologic scores. Labeled hUC-MSCs were located in the inflamed areas of colitis mice. Increases in regulatory T cells (Tregs) and CD5(+) B cells and decreases in Th1 cells, Th17 cells, and several pro-inflammatory cytokines were observed with hUC-MSC treatment. After adaptive transfer, CD5(+) B cells, which were located mainly in the peritoneal lavage fluid, improved TNBS-induced colitis by correcting Treg/Th1/Th17 imbalances. CD5(+) B cells also inhibited T-cell proliferation and produced interleukin (IL)-10.
  
  
  
  HUC-MSCs protected against experimental colitis by boosting the numbers of CD5(+) B cells and IL-10-producing CD5(+) Bregs, and correcting Treg/Th17/Th1 imbalances.
authors: Division of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, People's Republic of China.|Division of Gastroenterology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510655, People's Republic of China.
authors: Kang
authors: K
authors: Chao
authors: Division of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, People's Republic of China. shenghongzhang@163.com.
authors: Shenghong
authors: http://orcid.org/0000-0002-1647-0563
authors: S
authors: Zhang
authors: Division of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, People's Republic of China.
authors: Yun
authors: Y
authors: Qiu
authors: Center for Stem Cell Biology and Tissue Engineering, The Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-Sen University, Guangzhou, 510080, People's Republic of China.
authors: Xiaoyong
authors: X
authors: Chen
authors: Center for Stem Cell Biology and Tissue Engineering, The Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-Sen University, Guangzhou, 510080, People's Republic of China.
authors: Xiaoran
authors: X
authors: Zhang
authors: Center for Stem Cell Biology and Tissue Engineering, The Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-Sen University, Guangzhou, 510080, People's Republic of China.
authors: Chuang
authors: C
authors: Cai
authors: Center for Stem Cell Biology and Tissue Engineering, The Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-Sen University, Guangzhou, 510080, People's Republic of China.
authors: Yanwen
authors: Y
authors: Peng
authors: Division of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, People's Republic of China.
authors: Ren
authors: R
authors: Mao
authors: Department of Immunology, Weizmann Institute of Science, Rehovot, 7610001, Israel.
authors: Meirav
authors: M
authors: Pevsner-Fischer
authors: Division of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, People's Republic of China.
authors: Shomron
authors: S
authors: Ben-Horin
authors: Department of Immunology, Weizmann Institute of Science, Rehovot, 7610001, Israel.
authors: Eran
authors: E
authors: Elinav
authors: Division of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, People's Republic of China.
authors: Zhirong
authors: Z
authors: Zeng
authors: Division of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, People's Republic of China.
authors: Baili
authors: B
authors: Chen
authors: Division of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, People's Republic of China.
authors: Yao
authors: Y
authors: He
authors: Center for Stem Cell Biology and Tissue Engineering, The Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-Sen University, Guangzhou, 510080, People's Republic of China. xiangp@mail.sysu.edu.cn.
authors: Andy Peng
authors: AP
authors: Xiang
authors: Division of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, People's Republic of China. chenminhu@vip.163.com.
authors: Minhu
authors: M
authors: Chen
mesh_terms: D000818:Animals; D018956:CD5 Antigens / Q000276:immunology*; D049109:Cell Proliferation / Q000502:physiology; D003092:Colitis / Q000139:chemically induced / Q000276:immunology* / Q000628:therapy*; D004195:Disease Models, Animal; D006801:Humans; D007249:Inflammation / Q000276:immunology; D016753:Interleukin-10 / Q000276:immunology; D008297:Male; D059630:Mesenchymal Stem Cells / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D013234:Stem Cells / Q000276:immunology*; D015996:Survival Rate; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology; D058504:Th17 Cells / Q000276:immunology; D014302:Trinitrobenzenesulfonic Acid / Q000494:pharmacology; D014470:Umbilical Cord / Q000276:immunology*
chemical_list: D018956:CD5 Antigens; D016753:Interleukin-10; D014302:Trinitrobenzenesulfonic Acid
keywords: B regulatory cell; Colitis; Crohn’s disease; Mesenchymal stem cells; T helper cell