Role of T cells in malnutrition and obesity

Valerie A Gerriets, Nancie J MacIver, Valerie A Gerriets, Nancie J MacIver

Abstract

Nutritional status is critically important for immune cell function. While obesity is characterized by inflammation that promotes metabolic syndrome including cardiovascular disease and insulin resistance, malnutrition can result in immune cell defects and increased risk of mortality from infectious diseases. T cells play an important role in the immune adaptation to both obesity and malnutrition. T cells in obesity have been shown to have an early and critical role in inducing inflammation, accompanying the accumulation of inflammatory macrophages in obese adipose tissue, which are known to promote insulin resistance. How T cells are recruited to adipose tissue and activated in obesity is a topic of considerable interest. Conversely, T cell number is decreased in malnourished individuals, and T cells in the setting of malnutrition have decreased effector function and proliferative capacity. The adipokine leptin, which is secreted in proportion to adipocyte mass, may have a key role in mediating adipocyte-T cell interactions in both obesity and malnutrition, and has been shown to promote effector T cell function and metabolism while inhibiting regulatory T cell proliferation. Additionally, key molecular signals are involved in T cell metabolic adaptation during nutrient stress; among them, the metabolic regulator AMP kinase and the mammalian target of rapamycin have critical roles in regulating T cell number, function, and metabolism. In summary, understanding how T cell number and function are altered in obesity and malnutrition will lead to better understanding of and treatment for diseases where nutritional status determines clinical outcome.

Keywords: T cells; inflammation; leptin; malnutrition; obesity.

Figures

Figure 1
Figure 1
Adipose tissue is remodeled following high-fat diet-induced obesity. Multiple immune cells reside in adipose tissue. High-fat diet-induced obesity results in decreased regulatory T cells (Treg) and alternatively activated M2 macrophages. At the same time, there is an increase in adipose-resident inflammatory macrophages (classically activated M1 macrophages), CD4+ Th1 cells, CD8+ T cells, and B cells. The role of CD4+ Th2 and Th17 cells in adipose tissue in obesity is less certain.
Figure 2
Figure 2
Malnutrition leads to changes in adipocyte-secreted hormones and T cell number and function. Malnutrition leads to decreased adipocyte mass, which results in decreased circulating leptin. Concurrently, malnourished individuals show changes in CD4+ and CD8+ T cell number and function, leading to increased susceptibility to infection and protection against certain forms of autoimmunity. Leptin may mediate a subset of these malnutrition-related changes to T cell number and function, as leptin is known to alter CD4+ T cell number and cytokine production.
Figure 3
Figure 3
Nutritional status is critical for normal immune function. Malnutrition reduces immunity and increases markedly the risks and mortality from severe infections, whereas obesity heightens immune reactivity and predisposes to systemic inflammation that fosters the development of inflammatory disorders and insulin resistance leading to type 2 diabetes mellitus.

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