Toll-like receptors regulate B cell cytokine production in patients with diabetes

Abstract

Aims/hypothesis Understanding cellular and molecular events in diabetes mellitus will identify new approaches for therapy. Immune system cells are important modulators of chronic inflammation in diabetes mellitus, but the role of B cells is not adequately studied. The aim of this work was to define the function of B cells in diabetes mellitus patients through focus on B cell responses to pattern recognition receptors. Methods We measured expression and function of Toll-like receptors (TLRs) on peripheral blood B cells from diabetes mellitus patients by flow cytometry and multiplexed cytokine analysis. We similarly analysed B cells from non-diabetic donors and periodontal disease patients as comparative cohorts.

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

“…S2C), a murine ortholog of human IL-8. We conclude the proinflammatory B-cell cytokine profile in obese mice mirrors that in T2D subjects (2). Thus, B cells contribute to chronic inflammation in IR/T2D by constitutively and inducibly producing a proinflammatory cytokine profile.…”

“…Peripheral blood (50-100 mL) was collected into heparinized tubes by venous puncture, and cells were purified, cultured, stimulated, and harvested as previously described (2,11). CD19 − PBMCs were prepared by removing CD19 + B cells with positively selecting magnetic beads (Miltenyi) and were confirmed to be B cell depleted by flow analysis for CD19 + cells.…”

“…Work implicating B cells in IR/T2D is limited. We showed B cells from T2D subjects secrete a proinflammatory cytokine profile, including an extraordinary inability to secrete the potent anti-inflammatory cytokine IL-10 and an elevated production of proinflammatory IL-8 compared with B cells from non-T2D subjects (2). Given the importance of B-cell IL-10 in preventing numerous inflammatory diseases (3,4) and the links between IL-8 and T2D (5,6), these data suggest that altered B-cell cytokine production plays an important role in initiating or promoting IR/T2D.…”

Foxp3+t-Regulatory Lymphocytes and Autoantibodies in Patients With Arterial Hypertension, Associated With Diabetes Mellitus Type 2 and Impaired Glucose Tolerance

“…В большинстве случаев оба эти состояния ассо-циированы с артериальной гипертензией (АГ) [2]. В настоящее время считается, что в развитии СД 2-го типа и его осложнений, помимо собствен-но глюкозотоксичности и метаболических рас-стройств, принимает активное участие иммунное воспаление, однако взаимосвязи между этими па-тологическими процессами изучены недостаточ-но [9].…”

“…Было показано, что при СД 2-го типа на-рушается нормальное функционирование В-лимфоцитов, и тяжесть метаболических рас-стройств у пациентов коррелирует с содержа-нием иммуноглобулинов и иммунных комплек-сов в крови [9,15,18]. Известно, что ведущую роль в контроле активации эффекторных Т-и В-лимфоцитов играют FoxP3 + Т-регуляторные клетки (Treg) [16].…”