Immune ageing at single-cell resolution

Mogilenko, Denis A.; Shchukina, Irina; Artyomov, Maxim N.

doi:10.1038/s41577-021-00646-4

Cited by 175 publications

(185 citation statements)

References 204 publications

(364 reference statements)

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“…Although the markers used to distinguish this alternative B cell subset have not been firmly established, expression of the transcription factor T-bet, the integrin CD11c, different Fc receptor-like (FcRL) proteins, and chemokine receptors (such as CXCR3) have been used (27). This subset of B cells is present in healthy individuals at low levels (28) and increases with age (29), but also expands greatly during inflammatory conditions, including infections, autoimmune disorders, and after vaccination (30,31).…”

Section: Alternative B Cell Differentiation In Disease and Vaccinationmentioning

confidence: 99%

Alternative B Cell Differentiation During Infection and Inflammation

2022

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Long-term protective immunity to infectious disease depends on cell-mediated and humoral immune responses. Induction of a strong humoral response relies on efficient B cell activation and differentiation to long-lived plasma cells and memory B cells. For many viral or bacterial infections, a single encounter is sufficient to induce such responses. In malaria, the induction of long-term immunity can take years of pathogen exposure to develop, if it occurs at all. This repeated pathogen exposure and suboptimal immune response coincide with the expansion of a subset of B cells, often termed atypical memory B cells. This subset is present at low levels in healthy individuals as well but it is observed to expand in an inflammatory context during acute and chronic infection, autoimmune diseases or certain immunodeficiencies. Therefore, it has been proposed that this subset is exhausted, dysfunctional, or potentially autoreactive, but its actual role has remained elusive. Recent reports have provided new information regarding both heterogeneity and expansion of these cells, in addition to indications on their potential role during normal immune responses to infection or vaccination. These new insights encourage us to rethink how and why they are generated and better understand their role in our complex immune system. In this review, we will focus on recent advances in our understanding of these enigmatic cells and highlight the remaining gaps that need to be filled.

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Section: Alternative B Cell Differentiation In Disease and Vaccinationmentioning

confidence: 99%

Alternative B Cell Differentiation During Infection and Inflammation

2022

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“…Several such candidates, including growth differentiation factor 15 (GDF15) (Tanaka et al, 2018), matrix metalloproteinase-1 (MMP1), stanniocalcin-1 (STC1), and serine protease inhibitors (SERPINs) have been discovered by proteomic analysis (Basisty et al, 2020). In parallel to large-scale clinical trials, novel technologies, such as spatial and single-cell transcriptomic analysis in combination with machinelearning algorithms, will help to identify molecular targets of the drugs, and expression patterns that are associated with senescence and immune aging in differing immune cell populations (Mogilenko et al, 2021).…”

Section: Dietary Restrictionmentioning

confidence: 99%

Autophagy takes it all – autophagy inducers target immune aging

Zinecker

Simon

2022

Disease Models &Amp; Mechanisms

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Autophagy, as the key nutrient recycling pathway, enables eukaryotic cells to adapt to surging cellular stress during aging and, thereby, delays age-associated deterioration. Autophagic flux declines with age and, in turn, decreases in autophagy contribute to the aging process itself and promote senescence. Here, we outline how autophagy regulates immune aging and discuss autophagy-inducing interventions that target senescent immune cells, which are major drivers of systemic aging. We examine how cutting-edge technologies, such as single-cell omics methods hold the promise to capture the complexity of molecular and cellular phenotypes associated with aging, driving the development of suitable putative biomarkers and clinical bioassays. Finally, we debate the urgency to initiate large-scale human clinical trials. We give special preference to small molecule probes and to dietary interventions that can extend healthy lifespan and are affordable for most of the world's population.

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“…A multitude of molecular mechanisms are involved in the generation of TASP, signifying the involvement of almost all fundamental cellular mechanisms that maintain homeostasis and allow the cell to adapt to acute and chronic stressors. T cells from older adults exhibit variations in cell cycle dynamics, energy production and utilization, handling of cellular garbage, cellular differentiation and lineage commitment, regulation of cell motility and trafficking, and engagement of cell death pathways ( Sikora, 2015 ; Mogilenko et al, 2021a ). As expected, multiple signaling pathways, transcription factor networks, metabolic programs, deviations in the DNA repair machinery and epigenetic regulations have been implicated in bringing about TASP.…”

Section: Introductionmentioning

confidence: 99%

T-Cell Aging-Associated Phenotypes in Autoimmune Disease

et al. 2022

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The aging process causes profound restructuring of the host immune system, typically associated with declining host protection against cancer and infection. In the case of T cells, aging leads to the accumulation of a diverse set of T-cell aging-associated phenotypes (TASP), some of which have been implicated in driving tissue inflammation in autoimmune diseases. T cell aging as a risk determinant for autoimmunity is exemplified in two classical autoimmune conditions: rheumatoid arthritis (RA), a disease predominantly affecting postmenopausal women, and giant cell arteritis (GCA), an inflammatory vasculopathy exclusively occurring during the 6th–9th decade of life. Pathogenic T cells in RA emerge as a consequence of premature immune aging. They have shortening and fragility of telomeric DNA ends and instability of mitochondrial DNA. As a result, they produce a distinct profile of metabolites, disproportionally expand their endoplasmic reticulum (ER) membranes and release excess amounts of pro-inflammatory effector cytokines. Characteristically, they are tissue invasive, activate the inflammasome and die a pyroptotic death. Patients with GCA expand pathogenic CD4+ T cells due to aberrant expression of the co-stimulatory receptor NOTCH1 and the failure of the PD-1/PD-L1 immune checkpoint. In addition, GCA patients lose anti-inflammatory Treg cells, promoting tissue-destructive granulomatous vasculitis. In summary, emerging data identify T cell aging as a risk factor for autoimmune disease and directly link TASPs to the breakdown of T cell tolerance and T-cell-induced tissue inflammation.

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Immune ageing at single-cell resolution

Cited by 175 publications

References 204 publications

Alternative B Cell Differentiation During Infection and Inflammation

Alternative B Cell Differentiation During Infection and Inflammation

Autophagy takes it all – autophagy inducers target immune aging

T-Cell Aging-Associated Phenotypes in Autoimmune Disease

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