Title |
Regulatory B cells control T-cell autoimmunity through IL-21-dependent cognate interactions
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Published in |
Nature, October 2012
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DOI | 10.1038/nature11501 |
Pubmed ID | |
Authors |
Ayumi Yoshizaki, Tomomitsu Miyagaki, David J. DiLillo, Takashi Matsushita, Mayuka Horikawa, Evgueni I. Kountikov, Rosanne Spolski, Jonathan C. Poe, Warren J. Leonard, Thomas F. Tedder |
Abstract |
B cells regulate immune responses by producing antigen-specific antibodies. However, specific B-cell subsets can also negatively regulate T-cell immune responses, and have been termed regulatory B cells. Human and mouse regulatory B cells (B10 cells) with the ability to express the inhibitory cytokine interleukin-10 (IL-10) have been identified. Although rare, B10 cells are potent negative regulators of antigen-specific inflammation and T-cell-dependent autoimmune diseases in mice. How B10-cell IL-10 production and regulation of antigen-specific immune responses are controlled in vivo without inducing systemic immunosuppression is unknown. Using a mouse model for multiple sclerosis, here we show that B10-cell maturation into functional IL-10-secreting effector cells that inhibit in vivo autoimmune disease requires IL-21 and CD40-dependent cognate interactions with T cells. Moreover, the ex vivo provision of CD40 and IL-21 receptor signals can drive B10-cell development and expansion by four-million-fold, and generate B10 effector cells producing IL-10 that markedly inhibit disease symptoms when transferred into mice with established autoimmune disease. The ex vivo expansion and reinfusion of autologous B10 cells may provide a novel and effective in vivo treatment for severe autoimmune diseases that are resistant to current therapies. |
X Demographics
Geographical breakdown
Country | Count | As % |
---|---|---|
United States | 2 | 67% |
Unknown | 1 | 33% |
Demographic breakdown
Type | Count | As % |
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Members of the public | 3 | 100% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
United States | 8 | 1% |
Japan | 3 | <1% |
Netherlands | 2 | <1% |
United Kingdom | 1 | <1% |
Canada | 1 | <1% |
Singapore | 1 | <1% |
Germany | 1 | <1% |
Spain | 1 | <1% |
Chile | 1 | <1% |
Other | 2 | <1% |
Unknown | 515 | 96% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 141 | 26% |
Researcher | 122 | 23% |
Student > Master | 51 | 10% |
Student > Bachelor | 39 | 7% |
Student > Doctoral Student | 32 | 6% |
Other | 84 | 16% |
Unknown | 67 | 13% |
Readers by discipline | Count | As % |
---|---|---|
Agricultural and Biological Sciences | 170 | 32% |
Medicine and Dentistry | 100 | 19% |
Immunology and Microbiology | 93 | 17% |
Biochemistry, Genetics and Molecular Biology | 38 | 7% |
Neuroscience | 10 | 2% |
Other | 43 | 8% |
Unknown | 82 | 15% |