Role of T Cells in Malnutrition and Obesity

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.

The CD4+ T cell regulatory network mediates inflammatory responses during acute hyperinsulinemia: a simulation study

“…The dynamical model and simulations provide a system-level analytical framework underlying observed cell behaviors and offer predictions that will require experimental validation [ Table 2]. Overall, our simulation study provides a platform to explain the relationship between hyperinsulinemia and altered stability and proportions of T regulatory cells that have been observed in adipose tissue [3,[36][37][38]40]. It also highlights and provides a dynamic explanation for the different roles of TGFβ and IL-10 [30][31][32][33].…”

“…Obesity-associated chronic inflammation is a complex phenomenon that results from the interaction between adipose tissue, hyperinsulinemia, and chronic inflammation [1][2][3][4]. Together, these linked conditions increase the risk to develop metabolic syndrome and type-2 diabetes mellitus.…”

“…In obese VAT murine models and humans, an enrichment of the Th1 and Th17 populations and a decrease in regulatory T cells has been described [3,[36][37][38]. Th1 and Th17 cells produce proinflammatory cytokines that inhibit insulin signalling.…”

“…The transcriptional profiles and functions of Tregs are also altered; by expressing proinflammatory cytokines like IFNγ and IL-17. This change in expression patterns causes Tregs to cluster with inflammatory T cells [3,[36][37][38]. While TGFβ is present in adipose tissue, its role in regulating Treg cells is still unclear, because the typical alterations caused by TGFβ are not observed in these cells [39].…”

“…These probably play important roles in the onset of inflammatory responses, and their systemic impact remains unresolved. A starting point, involves understanding: (i) the complex regulatory network involved in the cell fate attainment of CD4+ T cell types [11][12][13], (ii) how such network responds to extracellular metabolic and microenvironmental conditions [14,15], and (iii) how the resulting system dynamically modulates the inflammatory and immune responses [1][2][3][4].…”