Immunity & Ageing : I & A最新文献

Immunosenescence is the deterioration of the innate and adaptive immune systems associated with aging and is primarily characterized by a reduction in T cell production and accumulation of atypical subsets. Age-related immunological dysfunction leads to impaired immune protection and persistent low-grade chronic inflammation, resulting in a decreased vaccination response and increased vulnerability to infection, cancer, cardiovascular disease, and autoimmune disease in the elderly. As the elderly constitute a growing proportion of the population with renal disease, immunosenescence is a normal aging process that is prevalent among older people. In addition, immunosenescence seems to be more pronounced in patients with kidney diseases than in healthy controls, as shown by severe chronic inflammation, accumulation of immune cells with the senescent phenotype (CD28^- T cells, CD14⁺CD16⁺ monocytes), and proinflammatory cytokine production. Immunosenescence inhibits immunological clearance and renal tissue regeneration, thereby increasing the risk of permanent renal damage, infection, and cardiovascular events in patients with kidney disease, lowering the prognosis, and even influencing the efficacy of renal replacement treatment. Biological drugs (senomorphics and senolytics) target the aging immune system and exert renoprotective effects. This review aims to emphasize the features of immunosenescence and its influence on kidney diseases and immunotherapy, highlighting the future directions of kidney disease treatment using senescence-focused techniques.

Immunosenescence is an age-dependent decline in immune functions and hallmark of aging in diverse species, ranging from invertebrates to mammals. However, identifying the factors responsible for immunosenescence is challenging because of the complexity of immune systems and aging in mammals. The roundworm Caenorhabditis elegans is suitable for understanding immunosenescence because of its simple immune system and rapid aging process. In this review, we discuss the advances in our understanding of immunosenescence in C. elegans. PMK-1/p38 mitogen-activated protein kinase (MAPK), SKN-1/NRF, and ZIP-10/bZIP transcription factor regulate immunosenescence through p38 MAPK and insulin/IGF-1 signaling pathways. Because these factors and pathways are evolutionarily conserved, the findings discussed in this review may help understand the mechanisms underlying immunosenescence and develop new treatment therapy for immunosenescence in humans.

Background: Statins have been widely used to prevent cardiovascular disease in middle-aged and elderly populations; however, the effect of long-term treatment on cognitive function is controversial. To simulate clinical conditions, middle-aged rats were given atorvastatin for 9 consecutive months to investigate the effect on natural cognitive decline and the possible mechanisms.

Results: The results showed that compared with the control group, long-term atorvastatin treatment naturally improved cognitive decline. Furthermore, long-term treatment regulated intestinal retinoic acid (RA) metabolism and storage by altering retinol dehydrogenase 7 (Rdh7) expression in the intestine, while RA metabolism affected the proliferation of intestinal T_reg cells and inhibited IL-17⁺γδ T-cell function. In addition, long-term atorvastatin increased intestinal flora richness and decreased IL-17 expression in hippocampal tissue.

Conclusion: Collectively, these findings provide the first evidence that long-term atorvastatin intervention may prevent cognitive decline in naturally ageing rats by inhibiting neuroinflammation via the gut-brain axis.

Background: Patients with systemic lupus erythematosus (SLE) are highly susceptible to infection and cardiovascular events, suggesting that chronic antigenic stimulation may accelerate premature aging in SLE patients. Premature aging in SLE is often accompanied with the expansion of cytotoxic CD4 + CD28-T cells. Damage caused by CD4 + CD28- T cells enhances the progressive aging of the tissue function and loss of organism's fitness. The high serum level of IL-15 has been implicated in the pathogenesis of SLE, but its role in CD4 + CD28-T cell-mediated cytotoxicity in nephritic SLE remains unclear. The aim of this study was to investigate the effect of IL-15 on functional properties and associated renal damage of cytotoxic CD4 + CD28- T cell in lupus nephritis (LN).

Results: Flow cytometry showed that the number of circulating innate-like CD4 + CD28- T cells was increased in patients with nephritic SLE. Immunofluorescence showed CD4 + CD28- T cell infiltration in the kidney of LN patients, which was correlated with multiple clinicopathological features including estimated glomerular filtration rate (eGFR), proteinuria, the proportion of glomerulosclerosis and the degree of renal chronicity. In addition, a high level of IL-15 and IL15-expressing macrophage infiltration was detected in the periglomerular and intraglomerular tissues of LN patients, which enhanced the innate features, cytokine secretion and migratory capability of CD4 + CD28- T cells, and finally exerted direct TCR-independent cytotoxicity on glomerular endothelial cells in an IL-15-dependent manner in vitro.

Conclusion: Our study demonstrated that excessive IL-15 potentially promoted cytotoxic CD4 + CD28- T cell-mediated renal damage in LN. This finding may provide new insights into the potential association of premature aging and tissue damage in LN.

Background: Vaccine efficiency has a significant role in the public perception of vaccination. The current study was designed to evaluate the efficacy of COVID-19 vaccines (AZD-1222, Sputnik-V, Sinopharm, and Covaxin) and the effect of gender on vaccine efficacy. We evaluated the efficacy of these vaccines among 214 health care employees in Iran. Blood samples were taken from all participants on day 0 and 14 days after the second dose. Humoral responses were evaluated by the PT-SARS-CoV-2-Neutralizing-Ab-96.

Results: The frequency of immunized individuals in the Sputnik V and AZD-1222 groups was 91% and 86%, respectively. This rate was 61% and 67% for Sinopharm and Covaxin vaccines. A comparison of the results obtained from the effectiveness of the vaccines between female and male groups did not demonstrate a significant difference.

Conclusion: According to the results, Sputnik V and AZD-1222 vaccines were more effective than Sinopharm and Covaxin vaccines. Moreover, the effectiveness of these vaccines is not related to gender.

Immune cells infiltrating the central nervous system (CNS) are involved in the defense against invading microbes as well as in the pathogenesis of neuroinflammatory diseases. In these conditions, the presence of several types of immune and inflammatory cells have been demonstrated. However, some studies have also reported low amounts of immune cells that have been detected in the CNS of healthy individuals, but the cell types present have not been systematically analyzed. To do this, we now used brain samples from The Genotype- Tissue Expression (GTEx) project to analyze the relative abundance of 22 infiltrating leukocyte types using a digital cytometry tool (CIBERSORTx). To characterize cell proportions in different parts of the CNS, samples from 13 different anatomic brain regions were used. The data obtained demonstrated that several leukocyte types were present in the CNS. Six leukocyte types (CD4 memory resting T cells, M0 macrophages, plasma cells, CD8 T cells, CD4 memory activated T cells, and monocytes) were present with a proportion higher than 0.05, i.e. 5%. These six cell types were present in most brain regions with only insignificant variation. A consistent association with age was seen with monocytes, CD8 T cells, and follicular helper T cells. Taken together, these data show that several infiltrating immune cell types are present in the non-diseased CNS tissue and that the proportions of infiltrating cells are affected by age in a manner that is consistent with literature on immunosenecence and inflammaging.

Microglia are immune-competent cells that are critically involved in maintaining normal brain function. A prominent characteristic of Alzheimer disease (AD) is microglial proliferation and activation concentrated around amyloid plaques in the brain. Recent research has revealed numerous microglial phenotypes related to aging and AD, apart from the traditional M1 and M2 types. Redox signalling modulates the acquisition of the classical or alternative microglia activation phenotypes. The numerous microglial functions can be achieved through these multiple phenotypes, which are associated with distinct molecular signatures.