Adaptive immunity and adipose tissue biology

Abstract

Studies of immunity typically focus on understanding how hematopoietic cells interact within conventional secondary lymphoid tissues. However, immune reactions and their regulation occur in various environments within the body. Adipose tissue is one context that can influence and be influenced by adjacent and embedded lymphocytes. Despite the abundance and wide distribution of such tissue, and despite a growing obesity epidemic, studies of these interactions have been only marginally appreciated in the past. Here, we review advances in understanding of lymphoid structures within adipose tissue, the relationship between adipose tissue and adaptive immune function, and evidence for how this relationship contributes to obesity-associated diseases.

Lymphocytes in obesity-related adipose tissue inflammation

“…These effects of leptin on adaptive immunity could provide a common factor linking obesity to autoimmunity and/or cancer. Intriguingly, ob/ob leptin-deficient mice have a reduced susceptibility to arthritis, experimental autoimmune encephalomyelitis and type 1 diabetes (in the NOD mouse model) [6,7,19]. As already mentioned, this effect could be attributed to the enhanced proliferation of Tregs in leptin-deficient mice [59][60][61].…”

“…Thus, leptin can affect T cell activation by stimulating the development of a Th1 (characterised by IFN-γ or TNF-α production) rather than a Th2 phenotype (characterised by the production of IL-4). Leptin increases IL-2 secretion in conventional T cells and may inhibit T cell apoptosis [6,19]. Furthermore, the presence of leptin receptor in the thymic environment is essential for T cell development, as shown in db/db mice [70].…”

“…The ob/ob leptin-deficient mice are characterised by hyperphagia, hyperglycaemia, hyperinsulinaemia and insulin resistance [69]. However, leptin levels are increased in humans and in other mouse models of obesity, indicating that leptin resistance is taking place [6]. Besides the unequivocal metabolic role of leptin, which overall prevents obesity, recent evidence points to immuno-modulatory actions of this hormone.…”

“…These adipokines orchestrate the expression and function of a complex network of chemokines and cytokines that regulate the accumulation of inflammatory cells in the WAT and, thereby, the development of WAT inflammation. Leptin levels increase with body mass and can, for example, stimulate the production of proinflammatory factors, such as TNF-α (also known as TNF), IL-6 and C-C motif chemokine ligands (CCLs), as well as reactive oxygen species in macrophages and mediate the activation of monocytes/macrophages and T cells [5][6][7]. In contrast, adiponectin, levels of which are decreased in obese individuals, exerts rather anti-inflammatory activities and ameliorates insulin resistance through an increase in NEFA oxidation and glucose uptake [8].…”

Abrogation of adenosine A1 receptor signalling improves metabolic regulation in mice by modulating oxidative stress and inflammatory responses

“…Thus, the beneficial effect of eliminating A 1 receptor signalling was extended to the hormone status. Increased leptin concentration or resistance were suggested as contributing to the inflammatory status in adipose tissue [31] and have been linked to ageassociated disorders including obesity, cardiovascular diseases, the metabolic syndrome and diabetes [32][33][34][35][36]. Elevated glucagon levels and insulin resistance are generally thought to contribute to the pathophysiology of hyperglycaemia in individuals with type 2 diabetes.…”