Homeostasis and the functional roles of CD4+ Treg cells in aging

Чуров, А. В.; Mamashov, Kylymbek Y.; Novitskaia, Anastasiia V.

doi:10.1016/j.imlet.2020.07.004

Cited by 29 publications

(27 citation statements)

References 82 publications

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“…Additionally, in contrast to the reduced naïve TC count, we observed an increase of Treg proportions with aging ( Fig. 2 H ), consistent with previous research ( 15 ). Moreover, OM exhibited a higher proportion of proliferating mitotic TC (T-mito) among the TC population.…”

Section: Resultssupporting

confidence: 92%

Effects of sex and aging on the immune cell landscape as assessed by single-cell transcriptomic analysis

Huang

Chen

Liu

et al. 2021

Proc. Natl. Acad. Sci. U.S.A.

122

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Sex and aging influence the human immune system, resulting in disparate responses to infection, autoimmunity, and cancer. However, the impact of sex and aging on the immune system is not yet fully elucidated. Using small conditional RNA sequencing, we found that females had a lower percentage of natural killer (NK) cells and a higher percentage of plasma cells in peripheral blood compared with males. Bioinformatics revealed that young females exhibited an overrepresentation of pathways that relate to T and B cell activation. Moreover, cell–cell communication analysis revealed evidence of increased activity of the BAFF/APRIL systems in females. Notably, aging increased the percentage of monocytes and reduced the percentage of naïve T cells in the blood and the number of differentially expressed genes between the sexes. Aged males expressed higher levels of inflammatory genes. Collectively, the results suggest that females have more plasma cells in the circulation and a stronger BAFF/APRIL system, which is consistent with a stronger adaptive immune response. In contrast, males have a higher percentage of NK cells in blood and a higher expression of certain proinflammatory genes. Overall, this work expands our knowledge of sex differences in the immune system in humans.

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Section: Resultssupporting

confidence: 92%

Effects of sex and aging on the immune cell landscape as assessed by single-cell transcriptomic analysis

Huang

Chen

Liu

et al. 2021

Proc. Natl. Acad. Sci. U.S.A.

122

View full text Add to dashboard Cite

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“…Estriol and chorionic gonadotropin positively affect Foxp3 expression and increase Treg frequency. Steroids and glucocorticoids can enlarge Treg populations in the periphery stimulating their function ( 111 ). In fact, Treg lacking the glucocorticoid receptor lose their suppressive function turning into Th1-like, IFNγ-producing cells in a murine colitis model ( 112 ).…”

Section: Treg Homeostasis and Function In Agingmentioning

confidence: 99%

“…This accumulation of antigen-specific Treg reduces clonal diversity which translates into a skewed aged Treg pool which can suppress only certain T cells while leaving the rest unaffected. This might favor some proinflammatory cells to remain active in aged hosts ( 111 ).…”

Section: Treg Homeostasis and Function In Agingmentioning

confidence: 99%

The Complex Role of Regulatory T Cells in Immunity and Aging

et al. 2021

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The immune system is a tightly regulated network which allows the development of defense mechanisms against foreign antigens and tolerance toward self-antigens. Regulatory T cells (Treg) contribute to immune homeostasis by maintaining unresponsiveness to self-antigens and suppressing exaggerated immune responses. Dysregulation of any of these processes can lead to serious consequences. Classically, Treg cell functions have been described in CD4+ T cells, but other immune cells also harbour the capacity to modulate immune responses. Regulatory functions have been described for different CD8+ T cell subsets, as well as other T cells such as γδT cells or NKT cells. In this review we describe the diverse populations of Treg cells and their role in different scenarios. Special attention is paid to the aging process, which is characterized by an altered composition of immune cells. Treg cells can contribute to the development of various age-related diseases but they are poorly characterized in aged individuals. The huge diversity of cells that display immune modulatory functions and the lack of universal markers to identify Treg make the expanding field of Treg research complex and challenging. There are still many open questions that need to be answered to solve the enigma of regulatory T cells.

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“…In inflammaging, innate immune cells such as macrophages are continuously activated with increased secretion of pro‐inflammatory cytokines including IL‐6, IL‐8 and IL‐1β, as well as a balance towards immunosenescence 73 . The compositions of Treg cells are changed in an aged population with increased natural Treg cells but decreased inducible Treg cells 74 ,. 75 The dysfunctions of older Treg cells are indicated by increased incidences of excessive immune diseases such as autoimmune diseases and cancer.…”

Section: Gut Dysbiosis Linked To Risk Factors Of Severe Covid‐19mentioning

confidence: 99%

Altered gut microbial metabolites could mediate the effects of risk factors in Covid‐19

Chen¹,

Hall²,

Vitetta

2021

Reviews in Medical Virology

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Summary Coronavirus disease 2019 (Covid‐19), caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection, is now pandemic. While most Covid‐19 patients will experience mild symptoms, a small proportion will develop severe disease, which could be fatal. Clinically, Covid‐19 patients manifest fever with dry cough, fatigue and dyspnoea, and in severe cases develop into acute respiratory distress syndrome (ARDS), sepsis and multi‐organ failure. These severe patients are characterized by hyperinflammation with highly increased pro‐inflammatory cytokines including IL‐6, IL‐17 and TNF‐alpha as well as C‐reactive protein, which are accompanied by decreased lymphocyte counts. Clinical evidence supports that gut microbiota dysregulation is common in Covid‐19 and plays a key role in the pathogenesis of Covid‐19. In this narrative review, we summarize the roles of intestinal dysbiosis in Covid‐19 pathogenesis and posit that the associated mechanisms are being mediated by gut bacterial metabolites. Based on this premise, we propose possible clinical implications. Various risk factors could be causal for severe Covid‐19, and these include advanced age, concomitant chronic disease, SARS‐CoV‐2 infection of enterocytes, use of antibiotics and psychological distress. Gut dysbiosis is associated with risk factors and severe Covid‐19 due to decreased commensal microbial metabolites, which cause reduced anti‐inflammatory mechanisms and chronic low‐grade inflammation. The preconditioned immune dysregulation enables SARS‐CoV‐2 infection to progress to an uncontrolled hyperinflammatory response. Thus, a pre‐existing gut microbiota that is diverse and abundant could be beneficial for the prevention of severe Covid‐19, and supplementation with commensal microbial metabolites may facilitate and augment the treatment of severe Covid‐19.

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Homeostasis and the functional roles of CD4+ Treg cells in aging

Cited by 29 publications

References 82 publications

Effects of sex and aging on the immune cell landscape as assessed by single-cell transcriptomic analysis

Effects of sex and aging on the immune cell landscape as assessed by single-cell transcriptomic analysis

The Complex Role of Regulatory T Cells in Immunity and Aging

Altered gut microbial metabolites could mediate the effects of risk factors in Covid‐19

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