miR‐150 regulates adipose tissue B cell function by targeting the BCR signaling pathway

作者：Haiqing Wang, Alexander Tseng, Richard Chang, Yu‐Lieh Lin, Wei Ying, Beiyan Zhou · 发表于：The FASEB Journal · 年份：2016 · DOI：10.1096/fasebj.30.1_supplement.lb653 · 研究领域：Adipokines, Inflammation, and Metabolic Diseases、Adipose Tissue and Metabolism、Atherosclerosis and Cardiovascular Diseases

Metainflammation and insulin resistance are two hallmarks of obesity which contribute to the pathogenesis of obesity‐associated diseases, including type 2 diabetes and cardiovascular diseases. Expansion of visceral adipose tissue (VAT) is central to the development of obesity associated metabolic syndromes, characterized by adipocyte malfunction and altered tissue specific immune cell profiles. Adipose tissue immune cells vary in number and their responses to obese stress. The adipose tissue resident B cells population dramatically expands to approximately 20% of stromal cells within obese visceral adipose tissues; however, their functions in the adipose tissue niche are poorly elucidated. Here we report that miR‐150 modulates adipose tissue function by controlling activation of B cells and their interactions with other immune cells. miR‐150KO mice displayed exacerbated obesity‐associated tissue inflammation and systemic insulin resistance, which is recapitulated by adoptive transfer of B cells, but not purified immunoglobulin, into obese B null mice. Using purified cell populations and a co‐culture platform, we found that miR‐150KO B cells directly enhanced proinflammatory activation of adipose tissue T cells and macrophages through cell‐cell interactions, but not through cell‐autologous mechanisms. Furthermore, miR‐150KO B cells displayed significantly enhanced antigen presentation upon stimulation, ultimately leading to elevated inflammation and insulin resistance, compare...