title: Adipose Natural Regulatory B Cells Negatively Control Adipose Tissue Inflammation.
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 Bregcells 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 Bregcells ameliorated those effects. Adipose environmental factors, including CXCL12 and free fatty acids, support Bregcell function, and Bregcell fraction and function were reduced in adipose tissue from obese mice and humans. Our findings indicate that adipose tissue Bregcells are a naturally occurring regulatory B cell subset that maintains homeostasis within adipose tissue and that Bregcell dysfunction contributes pivotally to the progression of adipose tissue inflammation in obesity.
authors.affiliation: 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.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Nishimura
authors.affiliation: Department of Cardiovascular Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan. Electronic address: manabe-tky@umin.ac.jp.
authors.forename: Ichiro
authors.initials: I
authors.lastname: Manabe
authors.affiliation: Research Institute, National Center for Global Health and Medicine, Tokyo 162-8655, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Takaki
authors.affiliation: 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.
authors.forename: Mika
authors.initials: M
authors.lastname: Nagasaki
authors.affiliation: 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.
authors.forename: Makoto
authors.initials: M
authors.lastname: Otsu
authors.affiliation: Department of Cardiovascular Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Yamashita
authors.affiliation: Department of Cardiovascular Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan.
authors.forename: Junichi
authors.initials: J
authors.lastname: Sugita
authors.affiliation: Department of Plastic Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan.
authors.forename: Kotaro
authors.initials: K
authors.lastname: Yoshimura
authors.affiliation: Center for iPS Cell Research and Application, Kyoto University, Kyoto 606-8507, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Eto
authors.affiliation: Department of Cardiovascular Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan.
authors.forename: Issei
authors.initials: I
authors.lastname: Komuro
authors.affiliation: 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.
authors.forename: Takashi
authors.initials: T
authors.lastname: Kadowaki
authors.affiliation: Jichi Medical University, Tochigi 329-0498, Japan.
authors.forename: Ryozo
authors.initials: R
authors.lastname: Nagai