Abstract
BackgroundObesity has been associated with chronic inflammation and oxidative stress. Both conditions play a determinant role in the pathogenesis of age-related diseases, such as immunosenescence. Adipose tissue can modulate the function of the immune system with the secretion of molecules influencing the phenotype of immune cells. The importance of the bone marrow (BM) in the maintenance of antigen-experienced adaptive immune cells has been documented in mice. Recently, some groups have investigated the survival of effector/memory T cells in the human BM. Despite this, whether high body mass index (BMI) may affect immune cells in the BM and the production of molecules supporting the maintenance of these cells it is unknown.MethodsUsing flow cytometry, the frequency and the phenotype of immune cell populations were measured in paired BM and PB samples obtained from persons with different BMI. Furthermore, the expression of BM cytokines was assessed. The influence of cytomegalovirus (CMV) on T cell subsets was additionally considered, dividing the donors into the CMV− and CMV+ groups.ResultsOur study suggests that increased BMI may affect both the maintenance and the phenotype of adaptive immune cells in the BM. While the BM levels of IL-15 and IL-6, supporting the survival of highly differentiated T cells, and oxygen radicals increased in overweight persons, the production of IFNγ and TNF by CD8+ T cells was reduced. In addition, the frequency of B cells and CD4+ T cells positively correlated with BMI in the BM of CMV− persons. Finally, the frequency of several T cell subsets, and the expression of senescence/exhaustion markers within these subpopulations, were affected by BMI. In particular, the levels of bona fide memory T cells may be reduced in overweight persons.ConclusionOur work suggests that, in addition to aging and CMV, obesity may represent an additional risk factor for immunosenescence in adaptive immune cells. Metabolic interventions may help in improving the fitness of the immune system in the elderly.
Highlights
Obesity is characterized by excessive accumulation of subcutaneous adipose tissue and visceral fat, which impairs overall health and promotes the development of several pathologies, including age-related diseases
The expression of both IL-15 and IL-6 in bone marrow mononuclear cells (BMMCs) was higher in the group body mass index (BMI) > 30, in comparison with lean persons (BMI < 25) (Fig. 1a-b)
Levels of reactive oxygen species (ROS) and the proinflammatory molecules IFNγ and TNF increase in the Representative histograms showing the intensity of IL-15, IL-6 and DHE in donors with BMI < 25 (BMI = 23.2) and BMI > 30 (BMI = 34.6) are shown
Summary
Obesity is characterized by excessive accumulation of subcutaneous adipose tissue and visceral fat, which impairs overall health and promotes the development of several pathologies, including age-related diseases. It has been shown that obesity is a cause of oxidative stress and chronic inflammation throughout the body, conditions which play a major role in the pathogenesis of diseases [3, 4]. The expression of proinflammatory molecules IFNγ and TNF and the levels of reactive oxygen species (ROS) are high in the BM [14]. In this situation, the expression of IL-15 and IL-6, which support the survival of highly differentiated CD8+ T cell subsets in the BM, is increased. Obesity has been associated with chronic inflammation and oxidative stress Both conditions play a determinant role in the pathogenesis of age-related diseases, such as immunosenescence. Whether high body mass index (BMI) may affect immune cells in the BM and the production of molecules supporting the maintenance of these cells it is unknown
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