The impact of body mass index on adaptive immune cells in the human bone marrow

Abstract

Background: 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. 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. Methods: Using 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. Results: Our 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. Conclusion: Our 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.

T cell phenotypes associated with insulin resistance: results from the Berlin Aging Study II

“…Taken together, our findings thus imply that insulin resistance is associated with a higher “age” of circulating T cells. Since the serostatus of CMV can affect the phenotype of immune cell subsets as well [ 24 ], we additionally correlated the BMI and ISI OGTT with immune cell parameters from CMV seronegative and seropositive participants. We found that the correlation coefficients were influenced by the CMV serostatus and that some significant correlations between T cell subsets, BMI and ISI OGTT were found in CMV + , but not CMV − participants.…”

Obesity, Nutrients and the Immune System in the Era of COVID-19

“…Obesity therefore reduces the repertoire of circulating T cells and the repertoire of antigens to which they can respond. There is also a decrease in the size of the inguinal lymph nodes, a decrease in the number of circulating T cells, as well as a decrease in lymphatic circulation, which decreases the migration of dendritic cells to the peripheral lymph nodes [ 49 ].…”

“…Adiponectin deficiency contributes to this shift of macrophages from the anti-inflammatory M2 phenotype to the pro-inflammatory M1 phenotype. Thus, in the basal state, there is a chronic polarization into pro-inflammatory M1 macrophages [ 49 ]. Through chemokine secretion, these M1 macrophages will attract peripheral monocytes which will in turn differentiate into M1 macrophages [ 49 ].…”

“…Thus, in the basal state, there is a chronic polarization into pro-inflammatory M1 macrophages [ 49 ]. Through chemokine secretion, these M1 macrophages will attract peripheral monocytes which will in turn differentiate into M1 macrophages [ 49 ]. It can be noted that already in the basal state the circulating monocytes of obese patients have increased secretion of pro-inflammatory cytokines [ 52 ].…”

Involvement of Interleukin-1 Receptor-Associated Kinase 4 and Interferon Regulatory Factor 5 in the Immunopathogenesis of SARS-CoV-2 Infection: Implications for the Treatment of COVID-19

“…Chronic innate proinflammatory drive to the adaptive immune system in metabolic inflammation leads eventual to T cell exhaustion. Changes in T and B cell function in metabolic inflammation, as well as in the elderly and, more acutely, in COVID-19 are all broadly similar, in that innate function is relatively preserved, but T cell and B cell compartments exhibit features of "exhaustion" or "senescence" (73, 113,114). Therefore, pre-existing metabolic inflammation across a variety of chronic conditions presages an unfavorable course and outcome of COVID-19 (115,116).…”