B cells promote inflammation in obesity and type 2 diabetes through regulation of T-cell function and an inflammatory cytokine profile

J DeFuria, AC Belkina… - Proceedings of the …, 2013 - National Acad Sciences
J DeFuria, AC Belkina, M Jagannathan-Bogdan, J Snyder-Cappione, JD Carr…
Proceedings of the National Academy of Sciences, 2013National Acad Sciences
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 …
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.
National Acad Sciences