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Advanced Drug Delivery Reviews 2020Vaccines are one of the most powerful technologies supporting public health. The adaptive immune response induced by immunization arises following appropriate activation...
Vaccines are one of the most powerful technologies supporting public health. The adaptive immune response induced by immunization arises following appropriate activation and differentiation of T and B cells in lymph nodes. Among many parameters impacting the resulting immune response, the presence of antigen and inflammatory cues for an appropriate temporal duration within the lymph nodes, and further within appropriate subcompartments of the lymph nodes- the right timing and location- play a critical role in shaping cellular and humoral immunity. Here we review recent advances in our understanding of how vaccine kinetics and biodistribution impact adaptive immunity, and the underlying immunological mechanisms that govern these responses. We discuss emerging approaches to engineer these properties for future vaccines, with a focus on subunit vaccines.
Topics: Adjuvants, Immunologic; B-Lymphocytes; Drug Carriers; Humans; Immunity, Humoral; Inflammation Mediators; Liposomes; Lymph Nodes; Nanoparticles; Plasmids; RNA, Messenger; T-Lymphocytes; Tissue Distribution; Vaccines
PubMed: 32598970
DOI: 10.1016/j.addr.2020.06.019 -
Experimental Gerontology Jun 2023Ageing is associated with several physiological changes, including changes in the immune system. Age-related changes in the innate and adaptive immune system are thought... (Review)
Review
INTRODUCTION
Ageing is associated with several physiological changes, including changes in the immune system. Age-related changes in the innate and adaptive immune system are thought to contribute to frailty. Understanding the immunological determinants of frailty could help to develop and deliver more effective care to older people. This systematic review aims to study the association between biomarkers of the ageing immune system and frailty.
METHODS
The search strategy was performed in PubMed and Embase, using the keywords "immunosenescence", "inflammation", "inflammaging" and "frailty". We included studies that investigated the association of biomarkers of the ageing immune system and frailty cross-sectionally in older adults, without an active disease that affects immune parameters. Three independent researchers selected the studies and performed data extraction. Study quality was assessed using the Newcastle-Ottawa scale adapted for cross-sectional studies.
RESULTS
A total of 44 studies, with a median number of 184 participants, was included. Study quality was good in 16 (36 %), moderate in 25 (57 %) and poor in 3 (7 %) of studies. The most frequently studied inflammaging biomarkers were IL-6, CRP and TNF-α. Associations with frailty were observed for increased levels of (i) IL-6 in 12 of 24 studies, (ii) CRP in 7 of 19 studies, and (ii) TNF-α in 4 of 13 studies. In none of the other studies were associations observed of frailty with these biomarkers. Different types of T-lymphocyte subpopulations were studied but each subset was studied only once, and the study sample sizes were low.
CONCLUSION
Our review of 44 studies on the relation between immune biomarkers and frailty identified IL-6 and CRP as the biomarkers that were most consistently associated with frailty. T-lymphocyte subpopulations were investigated but too infrequently to draw strong conclusions yet, although initial results are promising. Additional studies are required in order to further validate these immune biomarkers in larger cohorts. Furthermore, prospective studies in more uniform settings and larger cohorts are needed to further investigate the association with immune candidate biomarkers for which potential associations with ageing and frailty were previously observed, before these can be used in clinical practice to help assess frailty and improve the care treatments of older patients.
Topics: Humans; Aged; Prospective Studies; Tumor Necrosis Factor-alpha; Cross-Sectional Studies; Interleukin-6; Aging; Frailty; Biomarkers; Immune System; Frail Elderly
PubMed: 37028607
DOI: 10.1016/j.exger.2023.112163 -
Frontiers in Immunology 2023Glutamate, as one of the most important carbon sources in the TCA cycle, is central in metabolic processes that will subsequently influence tumor progression. Several... (Review)
Review
Glutamate, as one of the most important carbon sources in the TCA cycle, is central in metabolic processes that will subsequently influence tumor progression. Several factors can affect the expression of glutamate receptors, playing either a tumor-promoting or tumor-suppressor role in cancer. Thus, the activation of glutamate receptors by the ligand could play a role in tumor development as ample studies have demonstrated the expression of glutamate receptors in a broad range of tumor cells. Glutamate and its receptors are involved in the regulation of different immune cells' development and function, as suggested by the receptor expression in immune cells. The activation of glutamate receptors can enhance the effectiveness of the effector's T cells, or decrease the cytokine production in immunosuppressive myeloid-derived suppressor cells, increasing the antitumor immune response. These receptors are essential for the interaction between tumor and immune cells within the tumor microenvironment (TME) and the regulation of antitumor immune responses. Although the role of glutamate in the TCA cycle has been well studied, few studies have deeply investigated the role of glutamate receptors in the regulation of cancer and immune cells within the TME. Here, by a systematic review of the available data, we will critically assess the physiopathological relevance of glutamate receptors in the regulation of cancer and immune cells in the TME and provide some unifying hypotheses for futures research on the role of glutamate receptors in the immune modulation of the tumor.
Topics: Humans; Tumor Microenvironment; Neoplasms; T-Lymphocytes; Glutamic Acid; Receptors, Glutamate
PubMed: 36817470
DOI: 10.3389/fimmu.2023.1123841 -
The Journal of Investigative Dermatology Nov 2022Because burn injuries are often followed by a derailed immune response and excessive inflammation, a thorough understanding of the occurring reactions is key to... (Meta-Analysis)
Meta-Analysis
Because burn injuries are often followed by a derailed immune response and excessive inflammation, a thorough understanding of the occurring reactions is key to preventing secondary complications. This systematic review, which includes 247 animal studies, shows the postburn response of 14 different immune cell types involved in immediate and long-term effects in both wound tissue and circulation. Peripheral blood neutrophil and monocyte numbers increased directly after burns, whereas thrombocyte numbers increased near the end of the first week. However, lymphocyte numbers were decreased for at least 2 weeks. In burn wound tissue, neutrophil and macrophage numbers accumulated during the first 3 weeks. Burns also altered cellular functions because we found an increased migratory potential of leukocytes, impaired antibacterial activity of neutrophils, and enhanced inflammatory mediator production by macrophages. Neutrophil surges were positively associated with burn size and were highest in rats. Altogether, this comprehensive overview of the temporal immune cell dynamics shows that unlike normal wound healing, burn injury induces a long-lasting inflammatory response. It provides a fundamental research basis to improve experimental set-ups, burn care, and outcomes.
Topics: Rats; Animals; Burns; Neutrophils; Macrophages; Anti-Bacterial Agents; Inflammation Mediators
PubMed: 35623415
DOI: 10.1016/j.jid.2022.05.004 -
Frontiers in Immunology 2022Patients with COVID-19 and tuberculosis coinfection are at an increased risk of severe disease and death. We therefore sought to evaluate the current evidence which...
BACKGROUND AND AIM
Patients with COVID-19 and tuberculosis coinfection are at an increased risk of severe disease and death. We therefore sought to evaluate the current evidence which assessed the immune response in COVID-19 and tuberculosis coinfection.
METHODS
We searched Pubmed/MEDLINE, EMBASE, Scopus, and Web of Science to identify articles published between 2020 and 2021. We included observational studies evaluating the immune response in patients with tuberculosis and COVID-19 compared to patients with COVID-19 alone.
RESULTS
Four cross-sectional studies (372 participants) were identified. In patients with asymptomatic COVID-19 and latent tuberculosis (LTBI), increased cytokines, chemokines, growth factors and humoral responses were found. In addition, patients with symptomatic COVID-19 and LTBI had higher leukocytes counts and less inflammation. Regarding patients with COVID-19 and active tuberculosis (aTB), they exhibited decreased total lymphocyte counts, CD4 T cells specific against SARS-CoV-2 and responsiveness to SARS-CoV-2 antigens compared to patients with only COVID-19.
CONCLUSION
Although the evidence is limited, an apparent positive immunomodulation is observed in patients with COVID-19 and LTBI. On the other hand, patients with COVID-19 and aTB present a dysregulated immune response. Longitudinal studies are needed to confirm these findings and expand knowledge.
Topics: COVID-19; Coinfection; Cross-Sectional Studies; Humans; Immunity; Latent Tuberculosis; SARS-CoV-2; Tuberculosis
PubMed: 36090983
DOI: 10.3389/fimmu.2022.992743 -
Frontiers in Immunology 2022Tic disorder is a neurodevelopmental disorder characterized by motor and phonic tic symptoms. Tourette syndrome (TS) is a subtype of tic disorder that shows more... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Tic disorder is a neurodevelopmental disorder characterized by motor and phonic tic symptoms. Tourette syndrome (TS) is a subtype of tic disorder that shows more persistent tic symptoms. The etiological mechanism of TS concerning immune dysfunction remains unclear due to limited evidence, especially for pediatric TS patients.
METHOD
In the present study, a meta-analysis was performed to confirm the identified changes in proinflammatory cytokines and T cells of pediatric TS patients. A total of five databases, including PubMed, Web of Science, PsycINFO, Google Scholar and the China National Knowledge Infrastructure (CNKI), were used for the literature search. The standardized mean difference (SMD) and mean difference (MD) with a 95% confidence interval (CI) were used to present the effect size of each type of proinflammatory cytokine and T cell. Sensitivity analysis, subgroup analysis and meta-regression analysis were used to explore the heterogeneity of the meta-analysis. This meta-analysis was registered in the International Platform of Registered Systematic Review and Meta-analysis Protocols (number: INPLASY2021110079).
RESULTS
In the 25 studies included in this meta-analysis, thirteen studies focused on the levels of T cells, and twelve studies focused on the levels of proinflammatory cytokines. Based on the random-effects model, the pooled MDs are -1.45 (95% CI: -3.44, 0.54) for CD3 cells, -4.44 (95% CI: -6.80, -2.08) for CD4 cells, and 1.94 (95% CI: -0.08, 3.97) for CD8 cells. The pooled SMDs are1.36 for IL-6 (95% CI: 0.00, 2.72) and 2.39 for tumor necrosis factor alpha (TNF-α) (95% CI: 0.93, 3.84).
CONCLUSION
We provided evidence of immune dysfunction in pediatric TS patients, with elevated levels of particular proinflammatory cytokines and disproportionate changes in T-cell subpopulations. Small to large effect sizes were identified for increased IL-6 levels as well as a reduced number of T helper cells, while a large effect size was identified for increased TNF-α levels. These results indicate a close association between peripheral immune activation and TS. However, the most direct and meaningful interaction between peripheral immune status and microglial activation in the central nervous system in TS patients requires further exploration.
Topics: Child; Cytokines; Humans; Interleukin-6; T-Lymphocytes; Tourette Syndrome; Tumor Necrosis Factor-alpha
PubMed: 35693824
DOI: 10.3389/fimmu.2022.843247 -
Biomolecules Jun 2022Muscle injuries are frequent in individuals with genetic myopathies and in athletes. Skeletal muscle regeneration depends on the activation and differentiation of... (Review)
Review
Muscle injuries are frequent in individuals with genetic myopathies and in athletes. Skeletal muscle regeneration depends on the activation and differentiation of satellite cells present in the basal lamina of muscle fibers. The skeletal muscle environment is critical for repair, metabolic and homeostatic function. Regulatory T cells (Treg) residing within skeletal muscle comprise a distinct and special cell population that modifies the inflammatory environment by secreting cytokines and amphiregulin, an epidermal growth factor receptor (EGFR) ligand that acts directly upon satellite cells, promoting tissue regeneration. This systematic review summarizes the current knowledge regarding the role of Treg in muscle repair and discusses their therapeutic potential in skeletal muscle injuries. A bibliographic search was carried out using the terms Treg and muscle regeneration and repair, covering all articles up to April 2021 indexed in the PubMed and EMBASE databases. The search included only published original research in human and experimental animal models, with further data analysis based on the PICO methodology, following PRISMA definitions and Cochrane guidelines.
Topics: Animals; Cell Differentiation; Humans; Muscle Fibers, Skeletal; Muscle, Skeletal; Muscular Diseases; T-Lymphocytes, Regulatory; Wound Healing
PubMed: 35740942
DOI: 10.3390/biom12060817 -
The Cochrane Database of Systematic... Jul 2017Lymphocytic colitis is a cause of chronic diarrhea. It is a subtype of microscopic colitis characterized by chronic, watery, non-bloody diarrhea and normal endoscopic... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Lymphocytic colitis is a cause of chronic diarrhea. It is a subtype of microscopic colitis characterized by chronic, watery, non-bloody diarrhea and normal endoscopic and radiologic findings. The etiology of this disorder is unknown.Therapy is based mainly on case series and uncontrolled trials, or by extrapolation of data for treating collagenous colitis, a related disorder. This review is an update of a previously published Cochrane review.
OBJECTIVES
To evaluate the efficacy and safety of treatments for clinically active lymphocytic colitis.
SEARCH METHODS
The MEDLINE, PUBMED and EMBASE databases were searched from inception to 11 August 2016 to identify relevant papers. Manual searches from the references of included studies and relevant review articles were performed.Abstracts from major gastroenterological meetings were also searched to identify research submitted in abstract form only. The trial registry web site www.ClinicalTrials.gov was searched to identify registered but unpublished trials. Finally, the Cochrane Central Register of Controlled Trials and the Cochrane Inflammatory Bowel Disease and Functional Bowel Disorders Group Specialized Trials Register were searched for other studies.
SELECTION CRITERIA
Randomized controlled trials assessing medical therapy for patients with biopsy-proven lymphocytic colitis were considered for inclusion DATA COLLECTION AND ANALYSIS: Data was independently extracted by at least two authors. Any disagreements were resolved by consensus. Data were analyzed on an intention-to-treat (ITT) basis. The primary outcome was clinical response as defined by the included studies. Secondary outcome measures included histological response as defined by the included studies, quality of life as measured by a validated instrument and the occurrence of adverse events. Risk ratios (RR) and 95% confidence intervals (CI) were calculated for dichotomous outcomes. The methodological quality of included studies was evaluated using the Cochrane risk of bias tool. The overall quality of the evidence supporting the primary outcome and selected secondary outcomes was assessed using the GRADE criteria. Data were combined for analysis if they assessed the same treatments. Dichotomous data were combined using a pooled RR along with corresponding 95% CI. A fixed-effect model was used for the pooled analysis.
MAIN RESULTS
Five RCTs (149 participants) met the inclusion criteria. These studies assessed bismuth subsalicylate versus placebo, budesonide versus placebo, mesalazine versus mesalazine plus cholestyramine and beclometasone dipropionate versus mesalazine. The study which assessed mesalazine versus mesalazine plus cholestyramine and the study which assessed beclometasone dipropionate versus mesalazine were judged to be at high risk of bias due to lack of blinding. The study which compared bismuth subsalicylate versus us placebo was judged as low quality due to a very small sample size and limited data. The other 3 studies were judged to be at low risk of bias. Budesonide (9 mg/day for 6 to 8 weeks) was significantly more effective than placebo for induction of clinical and histological response. Clinical response was noted in 88% of budesonide patients compared to 38% of placebo patients (2 studies; 57 participants; RR 2.03, 95% CI 1.25 to 3.33; GRADE = low). Histological response was noted in 78% of budesonide patients compared to 33% of placebo patients (2 studies; 39 patients; RR 2.44, 95% CI 1.13 to 5.28; GRADE = low). Forty-one patients were enrolled in the study assessing mesalazine (2.4 g/day) versus mesalazine plus cholestyramine (4 g/day). Clinical response was noted in 85% of patients in the mesalazine group compared to 86% of patients in the mesalazine plus cholestyramine group (RR 0.99, 95% CI 0.77 to 1.28; GRADE = low). Five patients were enrolled in the trial studying bismuth subsalicylate (nine 262 mg tablets daily for 8 weeks versus placebo). There were no differences in clinical (P=0.10) or histological responses (P=0.71) in patients treated with bismuth subsalicylate compared with placebo (GRADE = very low). Forty-six patients were enrolled in the trial studying beclometasone dipropionate (5 mg/day or 10 mg/day) versus mesalazine (2.4 g/day). There were no differences in clinical remission at 8 weeks (RR 0.97; 95% CI 0.75 to 1.24; GRADE = low) and 12 months of treatment (RR 1.29; 95% CI 0.40 to 4.18; GRADE = very low). Although patients receiving beclometasone dipropionate (84%) and mesalazine (86%) achieved clinical remission at 8 weeks, it was not maintained at 12 months (26% and 20%, respectively). Adverse events reported in the budesonide studies include nausea, vomiting, neck pain, abdominal pain, hyperhidrosis and headache. Nausea and skin rash were reported as adverse events in the mesalazine study. Adverse events in the beclometasone dipropionate trial include nausea, sleepiness and change of mood. No adverse events were reported in the bismuth subsalicylate study.
AUTHORS' CONCLUSIONS
Low quality evidence suggests that budesonide may be effective for the treatment of active lymphocytic colitis. This benefit needs to be confirmed by a large placebo -controlled trial. Low quality evidence also suggests that mesalazine with or without cholestyramine and beclometasone dipropionate may be effective for the treatment of lymphocytic colitis, however this needs to be confirmed by large placebo-controlled studies. No conclusions can be made regarding bismuth subsalicylate due to the very small number of patients in the study, Further trials studying interventions for lymphocytic colitis are warranted.
Topics: Anti-Inflammatory Agents; Antidiarrheals; Beclomethasone; Bismuth; Budesonide; Cholestyramine Resin; Colitis, Lymphocytic; Humans; Mesalamine; Organometallic Compounds; Randomized Controlled Trials as Topic; Salicylates
PubMed: 28702956
DOI: 10.1002/14651858.CD006096.pub4 -
Journal of Research in Medical Sciences... 2021Several studies have demonstrated that the genetic polymorphisms in the genes encoding immune regulatory molecules, namely cytotoxic T-lymphocyte-associated protein 4... (Review)
Review
Several studies have demonstrated that the genetic polymorphisms in the genes encoding immune regulatory molecules, namely cytotoxic T-lymphocyte-associated protein 4 (CTLA4) and CD28, play a fundamental role in susceptibility to rheumatoid arthritis (RA). Several disperse population studies have resulted in conflicting outcomes regarding the genetic polymorphisms in these genes and RA risk. This systematic review and meta-analysis study was performed to reach a conclusive understanding of the role of single-nucleotide polymorphisms (SNPs) of CTLA4-rs231775, CTLA4-rs5742909, and CD28-rs1980422 in susceptibility to RA. Databases (ISI Web of Science, MEDLINE/PubMed, and Scopus) were searched to find the case-control studies surveying the association of CTLA4 gene rs231775, CTLA4 gene rs5742909, and CD28 gene rs1980422 polymorphisms and RA susceptibility in different population until August 2020. Association comparison between the polymorphisms and RA proneness was assessed using pooled odds ratio (OR) and their corresponding 95% confidence interval. This study was conducted on 16 population studies, comprising 1078 RA patients and 1118 healthy controls for CTLA4-rs231775, 2193 RA patients and 2580 healthy controls for CTLA4-rs5742909, and 807 RA patients and 732 healthy controls for CD28-rs1980422. Analysis indicated that G-allele, GG and GA genotypes, and dominant model for rs231775, recessive model for rs5742909, and C-allele, CC and CT genotypes, and recessive model for rs1980422 were significantly associated with increased RA risk. This meta-analysis showed that genetic polymorphisms of both immune inhibitory and activating genes, including CTLA4-rs231775, CTLA4-rs5742909, and CD28-rs1980422 polymorphisms, may increase susceptibility to RA.
PubMed: 34221051
DOI: 10.4103/jrms.JRMS_567_20 -
International Journal of Environmental... Apr 2023The rate of new human immunodeficiency virus (HIV) infections globally is alarming. Although antiretroviral therapy (ART) improves the quality of life among this group... (Meta-Analysis)
Meta-Analysis Review
The rate of new human immunodeficiency virus (HIV) infections globally is alarming. Although antiretroviral therapy (ART) improves the quality of life among this group of patients, ARTs are associated with risk of cardiovascular diseases (CVD). Moreover, virally suppressed patients still experience immune activation associated with HIV migration from reservoir sites. Statins are widely recommended as therapeutic agents to control ART-related CVD; however, their impacts on the cluster of differentiation (CD)4 count and viral load are inconsistent. To assess the effect of statins on markers of HIV infections, immune activation and cholesterol, we thoroughly reviewed evidence from randomised controlled trials. We found 20 relevant trials from three databases with 1802 people living with HIV (PLHIV) on statin-placebo treatment. Our evidence showed no significant effect on CD4 T-cell count standardised mean difference (SMD): (-0.59, 95% confidence intervals (CI): (-1.38, 0.19), = 0.14) following statin intervention in PLHIV on ART. We also found no significant difference in baseline CD4 T-cell count (SD: (-0.01, 95%CI: (-0.25, 0.23), = 0.95). Our findings revealed no significant association between statins and risk of viral rebound in PLHIV with undetectable viral load risk ratio (RR): (1.01, 95% CI: (0.98, 1.04), = 0.65). Additionally, we found a significant increase in CD8CD38HLA-DR T-cells (SMD (1.10, 95% CI: (0.93, 1.28), < 0.00001) and CD4CD38HLA-DR T-cells (SMD (0.92, 95% CI: (0.32, 1.52), = 0.003). Finally, compared to placebo, statins significantly reduced total cholesterol (SMD: (-2.87, 95% CI: (-4.08, -1.65), < 0.0001)). Our results suggest that the statin lipid-lowering effect in PLHIV on ART may elevate immune activation without influencing the viral load and CD4 count. However, due to the limited evidence synthesised in this meta-analysis, we recommend that future powered trials with sufficient sample sizes evaluate statins' effect on CD4 count and viral load, especially in virally suppressed patients.
Topics: Humans; HIV Infections; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Quality of Life; HIV-1; HLA-DR Antigens; CD4 Lymphocyte Count; Cardiovascular Diseases; Cholesterol; Viral Load
PubMed: 37174188
DOI: 10.3390/ijerph20095668