Adaptive Immunity and Antigen‐Specific Activation in Obesity‐Associated Insulin Resistance

Abstract

Type 2 diabetes mellitus (T2D) is a metabolic disease that is strongly tied to obesity and often preceded by insulin resistance (IR). It has been established that chronic inflammation of hypertrophic adipose tissue depots in obese individuals leads to obesity-associated IR and is mediated by cells of the innate immune system, particularly macrophages. More recently, cells of the adaptive immune system, B and T lymphocytes, have also emerged as important regulators of glucose homeostasis, raising the intriguing possibility that antigen-driven immune responses play a role in disease. In this review, we critically evaluate the roles that various B and T cell subsets play in IR, and then we examine the data suggesting that antigen-driven mechanisms, such as antigen presentation and costimulation, may drive the activity of these lymphocytes.

Dual CCR2/5 Antagonist Attenuates Obesity‐Induced Insulin Resistance by Regulating Macrophage Recruitment and M1/M2 Status

“…Recent reports have shown that the infiltration of CD8+ T cells precedes M1‐polarized macrophage recruitment, and the interactions between T cells and macrophages are considered to constitute a maladaptive feed‐forward loop, which leads to adipose inflammation and insulin resistance . We also observed that PF4178903 specifically reduced the accumulation of CD8+ T cells but did not influence CD4+ T cells in adipose tissue (Figure D‐F).…”

Noninvasive fat quantification of the liver and pancreas may provide potential biomarkers of impaired glucose tolerance and type 2 diabetes

“…Type 2 diabetes mellitus (T2DM) afflicts ∼387 million people worldwide and has become a major threat to public health. [ 1 ] Features of T2DM include insulin resistance and pancreatic β-cell dysfunction. [ 2 , 3 ] The accumulation of fat in the liver and excessive accumulation of visceral adipose tissue are reported risk factors for insulin resistance.…”

Crosstalk Between Mast Cells and Adipocytes in Physiologic and Pathologic Conditions

“…Like the cells of innate immunity, orchestration of immune responses by cells of adaptive immunity determines the metabolism and biology of AT. IR is associated with increases in cell populations with a pro-inflammatory phenotype including Th1, Th17, CD8+ cytotoxic T cells, and B-2 over those cell populations with regulatory properties mainly Treg and B-1a [66]. IFNγ and IL-17 secreted by Th1 and Th17 cells, respectively activate the pro-inflammatory functions of macrophages through the release of TNF-α, IL-6, and IL-1.…”