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- Lei Shen
- Shanghai Institute of Immunology, Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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- Melissa Hui Yen Chng
- Department of Pathology, Stanford University School of Medicine, Stanford, CA
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- Michael N. Alonso
- Department of Pathology, Stanford University School of Medicine, Stanford, CA
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- Robert Yuan
- Department of Pathology, Stanford University School of Medicine, Stanford, CA
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- Daniel A. Winer
- Division of Cellular & Molecular Biology, Diabetes Research Group, Toronto General Research Institute (TGRI), University Health Network, Toronto, Ontario, Canada
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- Edgar G. Engleman
- Department of Pathology, Stanford University School of Medicine, Stanford, CA
説明
<jats:p>Obesity-associated insulin resistance, a common precursor of type 2 diabetes, is characterized by chronic inflammation of tissues, including visceral adipose tissue (VAT). Here we show that B-1a cells, a subpopulation of B lymphocytes, are novel and important regulators of this process. B-1a cells are reduced in frequency in obese high-fat diet (HFD)-fed mice, and EGFP interleukin-10 (IL-10) reporter mice show marked reductions in anti-inflammatory IL-10 production by B cells in vivo during obesity. In VAT, B-1a cells are the dominant producers of B cell–derived IL-10, contributing nearly half of the expressed IL-10 in vivo. Adoptive transfer of B-1a cells into HFD-fed B cell–deficient mice rapidly improves insulin resistance and glucose tolerance through IL-10 and polyclonal IgM-dependent mechanisms, whereas transfer of B-2 cells worsens metabolic disease. Genetic knockdown of B cell–activating factor (BAFF) in HFD-fed mice or treatment with a B-2 cell–depleting, B-1a cell–sparing anti-BAFF antibody attenuates insulin resistance. These findings establish B-1a cells as a new class of immune regulators that maintain metabolic homeostasis and suggest manipulation of these cells as a potential therapy for insulin resistance.</jats:p>
収録刊行物
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- Diabetes
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Diabetes 64 (2), 593-603, 2014-09-22
American Diabetes Association