B cells promote inflammation in obesity and type 2 diabetes through regulation of T-cell function and an inflammatory cytokine profile
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- Jason DeFuria
- Department of Microbiology,
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- Anna C. Belkina
- Cancer Research Center, and
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- Madhumita Jagannathan-Bogdan
- Department of Pathology, Boston University School of Medicine, Boston, MA 02118;
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- Jennifer Snyder-Cappione
- Department of Microbiology,
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- Jordan David Carr
- Department of Microbiology,
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- Yanina R. Nersesova
- Section of Endocrinology, Diabetes, Nutrition and Weight Management, Department of Medicine, Boston Medical Center, Boston, MA 02118;
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- Douglas Markham
- Department of Microbiology,
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- Katherine J. Strissel
- The Obesity and Metabolism Laboratory, Jean Mayer U.S. Department of Agriculture Human Nutrition Research Center on Aging, Tufts University, Boston, MA 02111; and
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- Amanda A. Watkins
- Renal Section and
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- Min Zhu
- Department of Microbiology,
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- Jessica Allen
- Department of Pathology, Boston University School of Medicine, Boston, MA 02118;
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- Jacqueline Bouchard
- Department of Pathology, Boston University School of Medicine, Boston, MA 02118;
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- Gianluca Toraldo
- Section of Endocrinology, Diabetes, Nutrition and Weight Management, Department of Medicine, Boston Medical Center, Boston, MA 02118;
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- Ravi Jasuja
- Section of Endocrinology, Diabetes, Nutrition and Weight Management, Department of Medicine, Boston Medical Center, Boston, MA 02118;
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- Martin S. Obin
- The Obesity and Metabolism Laboratory, Jean Mayer U.S. Department of Agriculture Human Nutrition Research Center on Aging, Tufts University, Boston, MA 02111; and
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- Marie E. McDonnell
- Section of Endocrinology, Diabetes, Nutrition and Weight Management, Department of Medicine, Boston Medical Center, Boston, MA 02118;
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- Caroline Apovian
- Section of Endocrinology, Diabetes, Nutrition and Weight Management, Department of Medicine, Boston Medical Center, Boston, MA 02118;
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- Gerald V. Denis
- Cancer Research Center, and
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- Barbara S. Nikolajczyk
- Department of Microbiology,
書誌事項
- 公開日
- 2013-03-11
- DOI
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- 10.1073/pnas.1215840110
- 公開者
- Proceedings of the National Academy of Sciences
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説明
<jats:p>Patients with type 2 diabetes (T2D) have disease-associated changes in B-cell function, but the role these changes play in disease pathogenesis is not well established. Data herein show B cells from obese mice produce a proinflammatory cytokine profile compared with B cells from lean mice. Complementary in vivo studies show that obese B cell–null mice have decreased systemic inflammation, inflammatory B- and T-cell cytokines, adipose tissue inflammation, and insulin resistance (IR) compared with obese WT mice. Reduced inflammation in obese/insulin resistant B cell–null mice associates with an increased percentage of anti-inflammatory regulatory T cells (Tregs). This increase contrasts with the sharply decreased percentage of Tregs in obese compared with lean WT mice and suggests that B cells may be critical regulators of T-cell functions previously shown to play important roles in IR. We demonstrate that B cells from T2D (but not non-T2D) subjects support proinflammatory T-cell function in obesity/T2D through contact-dependent mechanisms. In contrast, human monocytes increase proinflammatory T-cell cytokines in both T2D and non-T2D analyses. These data support the conclusion that B cells are critical regulators of inflammation in T2D due to their direct ability to promote proinflammatory T-cell function and secrete a proinflammatory cytokine profile. Thus, B cells are potential therapeutic targets for T2D.</jats:p>
収録刊行物
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- Proceedings of the National Academy of Sciences
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Proceedings of the National Academy of Sciences 110 (13), 5133-5138, 2013-03-11
Proceedings of the National Academy of Sciences