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Cell Metab. 2013 Nov 5;18(5):759-766. doi: 10.1016/j.cmet.2013.09.017. Epub 2013 Oct 24.

Adipose Natural Regulatory B Cells Negatively Control Adipose Tissue Inflammation.

Author information

1
Department of Cardiovascular Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan; Translational Systems Biology and Medicine Initiative, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan. Electronic address: snishi-tky@umin.ac.jp.
2
Department of Cardiovascular Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan. Electronic address: manabe-tky@umin.ac.jp.
3
Research Institute, National Center for Global Health and Medicine, Tokyo 162-8655, Japan.
4
Department of Cardiovascular Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan; Computational Diagnostic Radiology and Preventive Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan.
5
Division of Stem Cell Therapy and Stem Cell Bank, Center for Stem Cell Biology and Regenerative Medicine, Institute of Medical Science, The University of Tokyo, Tokyo 108-0071, Japan.
6
Department of Cardiovascular Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan.
7
Department of Plastic Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan.
8
Center for iPS Cell Research and Application, Kyoto University, Kyoto 606-8507, Japan.
9
Translational Systems Biology and Medicine Initiative, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan; Department of Metabolic Diseases, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan.
10
Jichi Medical University, Tochigi 329-0498, Japan.

Abstract

Distinct B cell populations, designated regulatory B (Breg) cells, are known to restrain immune responses associated with autoimmune diseases. Additionally, obesity is known to induce local inflammation within adipose tissue that contributes to systemic metabolic abnormalities, but the underlying mechanisms that modulate adipose inflammation remain poorly understood. We identified Breg cells that produce interleukin-10 constitutively within adipose tissue. B cell-specific Il10 deletion enhanced adipose inflammation and insulin resistance in diet-induced obese mice, whereas adoptive transfer of adipose tissue Breg cells ameliorated those effects. Adipose environmental factors, including CXCL12 and free fatty acids, support Breg cell function, and Breg cell fraction and function were reduced in adipose tissue from obese mice and humans. Our findings indicate that adipose tissue Breg cells are a naturally occurring regulatory B cell subset that maintains homeostasis within adipose tissue and that Breg cell dysfunction contributes pivotally to the progression of adipose tissue inflammation in obesity.

PMID:
24209772
DOI:
10.1016/j.cmet.2013.09.017
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