title: T regulatory cells and B cells cooperate to form a regulatory loop that maintains gut homeostasis and suppresses dextran sulfate sodium-induced colitis.
abstract: Regulatory T cells (Tregs) and B cells present in gut-associated lymphoid tissues (GALT) are both implicated in the resolution of colitis. However, how the functions of these cells are coordinated remains elusive. We used the dextran sulfate sodium (DSS)-induced colitis model combined with gene-modified mice to monitor the progression of colitis, and simultaneously examine the number of Tregs and B cells, and the production of IgA antibodies. We found that DSS-treated mice exhibited more severe colitis in the absence of B cells, and that the adoptive transfer of B cells attenuated the disease. Moreover, the transfer of IL-10(-/-) B cells also attenuated colitis, suggesting that B cells inhibited colitis through an interleukin-10 (IL-10)-independent pathway. Furthermore, antibody depletion of Tregs resulted in exacerbated colitis. Intriguingly, the number of GALT Tregs in B cell-deficient mice was significantly decreased during colitis and the adoptive transfer of B cells into these mice restored the Treg numbers, indicating that B cells contribute to Treg homeostasis. We also found that B cells induced the proliferation of Tregs that in turn promoted B-cell differentiation into IgA-producing plasma cells. These results demonstrate that B cells and Tregs interact and cooperate to prevent excessive immune responses that can lead to colitis.
authors: Department of Immunology and Key Laboratory of Medical Molecular Virology of MOE/MOH, School of Basic Medical Sciences, Biotherapy Research Center of Fudan University, Shanghai, People's Republic of China.
authors: L
authors: L
authors: Wang
authors: BloodCenter of Wisconsin, Blood Research Institute, Milwaukee, Wisconsin, USA.
authors: A
authors: A
authors: Ray
authors: Department of Immunology and Key Laboratory of Medical Molecular Virology of MOE/MOH, School of Basic Medical Sciences, Biotherapy Research Center of Fudan University, Shanghai, People's Republic of China.
authors: X
authors: X
authors: Jiang
authors: Department of Immunology and Key Laboratory of Medical Molecular Virology of MOE/MOH, School of Basic Medical Sciences, Biotherapy Research Center of Fudan University, Shanghai, People's Republic of China.
authors: J-y
authors: JY
authors: Wang
authors: BloodCenter of Wisconsin, Blood Research Institute, Milwaukee, Wisconsin, USA.
authors: S
authors: S
authors: Basu
authors: Department of Immunology and Key Laboratory of Medical Molecular Virology of MOE/MOH, School of Basic Medical Sciences, Biotherapy Research Center of Fudan University, Shanghai, People's Republic of China.
authors: X
authors: X
authors: Liu
authors: Department of Immunology and Key Laboratory of Medical Molecular Virology of MOE/MOH, School of Basic Medical Sciences, Biotherapy Research Center of Fudan University, Shanghai, People's Republic of China.
authors: T
authors: T
authors: Qian
authors: Department of Immunology and Key Laboratory of Medical Molecular Virology of MOE/MOH, School of Basic Medical Sciences, Biotherapy Research Center of Fudan University, Shanghai, People's Republic of China.
authors: R
authors: R
authors: He
authors: BloodCenter of Wisconsin, Blood Research Institute, Milwaukee, Wisconsin, USA.
authors: B N
authors: BN
authors: Dittel
authors: Department of Immunology and Key Laboratory of Medical Molecular Virology of MOE/MOH, School of Basic Medical Sciences, Biotherapy Research Center of Fudan University, Shanghai, People's Republic of China.
authors: Y
authors: Y
authors: Chu
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D003092:Colitis / Q000276:immunology*; D016264:Dextran Sulfate / Q000633:toxicity; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006706:Homeostasis / Q000276:immunology*; D007413:Intestinal Mucosa / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D016513:Mice, SCID; D010581:Peyer's Patches / Q000276:immunology; D016133:Polymerase Chain Reaction; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
chemical_list: D016264:Dextran Sulfate