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Frontiers in Immunology 2020The tripartite motif (TRIM) proteins have been intensively studied as essential modulators in various biological processes, especially in regulating a wide range of...
The tripartite motif (TRIM) proteins have been intensively studied as essential modulators in various biological processes, especially in regulating a wide range of signaling pathways involved in immune responses. Most TRIM proteins have E3 ubiquitin ligase activity, mediating polyubiquitination of target proteins. Emerging evidence demonstrates that TRIM proteins play important roles in innate immunity by regulating pattern recognition receptors, vital adaptor proteins, kinases, and transcription factors in innate immune signaling pathways. Additionally, the critical roles of TRIM proteins in adaptive immunity, especially in T cell development and activation, are increasingly appreciated. In this review, we aim to summarize the studies on TRIMs in both innate and adaptive immunity, focusing on their E3 ubiquitin ligase functions in pattern recognition receptor signaling pathways and T cell functions, shedding light on the developing new strategies for modulating innate and adaptive immune responses against invading pathogens and avoiding autoimmunity.
Topics: Adaptive Immunity; Animals; Humans; Immunity, Innate; Immunomodulation; Signal Transduction; T-Lymphocytes; Tripartite Motif Proteins; Ubiquitin-Protein Ligases; Ubiquitination
PubMed: 33117334
DOI: 10.3389/fimmu.2020.02157 -
Autoimmunity Reviews Jun 2023Giant cell arteritis is the most common form of large vessel vasculitis and preferentially involves large and medium-sized arteries in patients over the age of 50.... (Review)
Review
Giant cell arteritis is the most common form of large vessel vasculitis and preferentially involves large and medium-sized arteries in patients over the age of 50. Aggressive wall inflammation, neoangiogenesis and consecutive remodeling processes are the hallmark of the disease. Though etiology is unknown, cellular and humoral immunopathological processes are well understood. Matrix metalloproteinase-9 mediated tissue infiltration occurs through lysis of basal membranes in adventitial vessels. CD4+ cells attain residency in immunoprotected niches, differentiate into vasculitogenic effector cells and enforce further leukotaxis. Signaling pathways involve the NOTCH1-Jagged1 pathway opening vessel infiltration, CD28 mediated T-cell overstimulation, lost PD-1/PD-L1 co-inhibition and JAK/STAT signaling in interferon dependent responses. From a humoral perspective, IL-6 represents a classical cytokine and potential Th-cell differentiator whereas interferon-γ (IFN- γ) has been shown to induce chemokine ligands. Current therapies involve glucocorticoids, tocilizumab and methotrexate application. However, new agents, most notably JAK/STAT inhibitors, PD-1 agonists and MMP-9 blocking substances, are being evaluated in ongoing clinical trials.
Topics: Humans; Giant Cell Arteritis; Autoimmunity; Programmed Cell Death 1 Receptor; CD4-Positive T-Lymphocytes; Cytokines; Takayasu Arteritis
PubMed: 36990133
DOI: 10.1016/j.autrev.2023.103328 -
The American Journal of Tropical... Sep 2013Abstract. Current regulations stipulate a yellow fever (YF) booster every 10 years. We conducted a systematic review of the protective efficacy and duration of immunity... (Review)
Review
Abstract. Current regulations stipulate a yellow fever (YF) booster every 10 years. We conducted a systematic review of the protective efficacy and duration of immunity of YF vaccine in residents of disease-endemic areas and in travelers to assess the need for a booster in these two settings and in selected populations (human immunodeficiency virus-infected persons, infants, children, pregnant women, and severely malnourished persons). Thirty-six studies and 22 reports were included. We identified 12 studies of immunogenicity, 8 of duration of immunity, 8 of vaccine response in infants and children, 7 of human-immunodeficiency virus-infected persons, 2 of pregnant women, and 1 of severely malnourished children. Based on currently available data, a single dose of YF vaccine is highly immunogenic and confers sustained life-long protective immunity against YF. Therefore, a booster dose of YF vaccine is not needed. Special considerations for selected populations are detailed.
Topics: Antibody Formation; Humans; Immunity; Immunization, Secondary; Randomized Controlled Trials as Topic; Risk Factors; Vaccination; Yellow Fever; Yellow Fever Vaccine; Yellow fever virus
PubMed: 24006295
DOI: 10.4269/ajtmh.13-0264 -
Epidemiology and Infection Jul 2022The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, first notified in China, has spread around the world causing high morbidity and mortality,... (Review)
Review
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, first notified in China, has spread around the world causing high morbidity and mortality, which is due to factors such as the subversion of the immune response. The aims of the study are to summarise and present the immunopathological relationship of COVID-19 with innate immunity. This is a systematic review conducted by the National Library of Medicine - National Institutes of Health, USA (PUBMED), Latin American and Caribbean Literature on Health Sciences (LILACS), Medical Literature Analysis and Retrieval System Online (MEDLINE) and Scientific Electronic Library Online (SCIELO) databases with clinical trials, assays, case-controls, cohort studies, systematic reviews and meta-analyses between February 2020 and July 2021. The version 2 of the Cochrane risk-of-bias tool for RCTs (RoB 2), Joana Briggs Institute (JBI) Critical Appraisal (for the review articles) and the Risk of Bias in Non-randomised Studies of Interventions (ROBINS-I) tools were used to evaluate the quality and the risk of bias of the studies included in this review. The innate immune response through the generation of interferons, alternative pathways and complement system lectins and the joint action of innate immune cells and cytokines and chemokines lead to different clinical outcomes, taking into account the exacerbated inflammatory response and pathogenesis. Then, in addition to interacting as a bridge for adaptive immunity, the innate immune response plays an essential role in primary defense and is one of the starting points for immune evasion by SARS-CoV-2.
Topics: COVID-19; Humans; Immune Evasion; Immunity, Innate; Pandemics; SARS-CoV-2; United States
PubMed: 35843719
DOI: 10.1017/S095026882200125X -
Molecular Psychiatry Mar 2023Meta-analyses implicate immune dysfunction in depression confirming increased levels of circulating immune proteins (e.g., cytokines) in depression cases compared to... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Meta-analyses implicate immune dysfunction in depression confirming increased levels of circulating immune proteins (e.g., cytokines) in depression cases compared to controls. White blood cells (WBC) both produce and are influenced by cytokines, and play key roles in orchestrating innate and adaptive immune responses, but their role in depression remains unclear. Therefore, a systematic review of studies of various WBC subsets in depression is required for a greater understanding of the nature of immune dysfunction in this illness.
METHODS
We searched PubMed and PsycINFO databases (inception to 5 April 2022) and conducted a systematic review and meta-analysis of identified studies comparing absolute count and/or relative percentage of flow cytometry-derived WBC subsets between depression cases and controls. Selected studies were quality assessed. Random-effect meta-analysis was performed.
RESULTS
Thirty-three studies were included and 27 studies (n = 2277) were meta-analysed. We report an increase in mean absolute counts of WBC (seven studies; standardised mean difference [SMD] = 1.07; 95% CI, 0.61-1.53; P < 0.01; I = 64%), granulocytes (two studies; SMD = 2.07; 95% CI, 1.45-2.68; P < 0.01; I = 0%), neutrophils (four studies; SMD = 0.91; 95% CI, 0.23-1.58; P < 0.01; I = 82%), monocytes (seven studies; SMD = 0.60; 95% CI, 0.19-1.01; P < 0.01; I = 66%), CD4 helper T cells (11 studies; SMD = 0.30; 95% CI, 0.15-0.45; P < 0.01; I = 0%), natural killer cells (11 studies; SMD = 1.23; 95% CI, 0.38-2.08; P < 0.01; I = 95%), B cells (10 studies; SMD = 0.30; 95% CI, 0.03-0.57; P = 0.03; I = 56%), and activated T cells (eight studies; SMD = 0.45; 95% CI, 0.24-0.66; P < 0.01; I = 0%) in depression, compared to controls. Fewer studies reported relative percentage, indicating increased neutrophils and decreased total lymphocytes, Th1, and Th2 cells in depression.
CONCLUSIONS
Depression is characterised by widespread alterations in circulating myeloid and lymphoid cells, consistent with dysfunction in both innate and adaptive immunity. Immune cells could be useful biomarkers for illness subtyping and patient stratification in future immunotherapy trials of depression, along with cytokines, other biomarkers, and clinical measures.
Topics: Humans; Depression; Biomarkers
PubMed: 36577838
DOI: 10.1038/s41380-022-01919-7 -
Rheumatology Advances in Practice 2018Adaptive designs can enable highly sophisticated and efficient early phase trials, but the clinical inference from these trials is surrounded by complexity, and...
OBJECTIVE
Adaptive designs can enable highly sophisticated and efficient early phase trials, but the clinical inference from these trials is surrounded by complexity, and currently there is a paucity but steadily increasing amount of use of these designs in all fields of medicine. We aim to review early phase trials in RA to discover those that have used adaptive designs and benchmark trial characteristics.
METHODS
From an OVID search for journal articles reporting the results of early phase trials in rheumatology, 35 studies were found, with 9 subsequently excluded; 11 were added from manual searches and 19 from searching the references. Study characteristics were extracted from the 56 papers (describing 62 trials), including the number of arms, number of patients, the primary outcome and when it was measured.
RESULT
One early phase trial using an adaptive design was found. The benchmark early phase trial in RA is a phase II double-blinded randomized trial, with four arms (one control and three intervention), each with 34 patients, and ACR20 measured at 16 weeks as the primary outcome.
CONCLUSION
The one adaptive design reviewed here, and a simulation study found in the search, both indicate that adaptive designs can be applied to early phase trials in RA. We have described the benchmark, which the efficiency of early phase trials using an adaptive design needs to exceed. These efficient designs could drive down numbers required, time for data collection and thus cost. Changes have been suggested, but more needs to be done.
PubMed: 31431982
DOI: 10.1093/rap/rky045 -
Inflammation Research : Official... May 2024γδ T cells are a distinct subset of unconventional T cells, which link innate and adaptive immunity by secreting cytokines and interacting with other immune cells,... (Review)
Review
OBJECTIVE
γδ T cells are a distinct subset of unconventional T cells, which link innate and adaptive immunity by secreting cytokines and interacting with other immune cells, thereby modulating immune responses. As the first line of host defense, γδ T cells are essential for mucosal homeostasis and immune surveillance. When abnormally activated or impaired, γδ T cells can contribute to pathogenic processes. Accumulating evidence has revealed substantial impacts of γδ T cells on the pathogenesis of cancers, infections, and immune-inflammatory diseases. γδ T cells exhibit dual roles in cancers, promoting or inhibiting tumor growth, depending on their phenotypes and the clinical stage of cancers. During infections, γδ T cells exert high cytotoxic activity in infectious diseases, which is essential for combating bacterial and viral infections by recognizing foreign antigens and activating other immune cells. γδ T cells are also implicated in the onset and progression of immune-inflammatory diseases. However, the specific involvement and underlying mechanisms of γδ T cells in oral diseases have not been systematically discussed.
METHODS
We conducted a systematic literature review using the PubMed/MEDLINE databases to identify and analyze relevant literature on the roles of γδ T cells in oral diseases.
RESULTS
The literature review revealed that γδ T cells play a pivotal role in maintaining oral mucosal homeostasis and are involved in the pathogenesis of oral cancers, periodontal diseases, graft-versus-host disease (GVHD), oral lichen planus (OLP), and oral candidiasis. γδ T cells mainly influence various pathophysiological processes, such as anti-tumor activity, eradication of infection, and immune response regulation.
CONCLUSION
This review focuses on the involvement of γδ T cells in oral diseases, with a particular emphasis on the main functions and underlying mechanisms by which γδ T cells influence the pathogenesis and progression of these conditions. This review underscores the potential of γδ T cells as therapeutic targets in managing oral health issues.
Topics: Humans; Mouth Diseases; Animals; Receptors, Antigen, T-Cell, gamma-delta; Intraepithelial Lymphocytes; Graft vs Host Disease; T-Lymphocytes
PubMed: 38563967
DOI: 10.1007/s00011-024-01870-z -
Life (Basel, Switzerland) Aug 2021Antiphospholipid syndrome (APS) is an autoimmune disease characterized by autoreactive B and T cells against β2-glycoprotein I (B2GPI), with vascular thrombosis or... (Review)
Review
Antiphospholipid syndrome (APS) is an autoimmune disease characterized by autoreactive B and T cells against β2-glycoprotein I (B2GPI), with vascular thrombosis or obstetrical complications. Dendritic cells (DCs) are crucial in the generation of autoimmunity. Here, we conducted a comprehensive systematic review on the relationship between DC and APS. We performed a literature search of PubMed as of 26 March 2021. A total of 33 articles were extracted. DCs are pivotal in inducing inflammatory responses and orchestrating adaptive immunity. DCs contribute to the local inflammation regarding vascular thrombosis or obstetrical complications. Both B2GPI and antiphospholipid antibodies (aPL) can promote antigen presentation by DCs and the generation or maintenance of autoimmunity. In addition, plasmacytoid DC activation is enhanced by aPL, thereby augmenting the inflammatory response. In line with these findings, DC modulation appears promising as a future treatment for APS. In conclusion, our review indicated the crucial role of DCs in the pathogenesis of APS. Deeper understanding of the complex relationship would help in developing new treatment strategies.
PubMed: 34440545
DOI: 10.3390/life11080801 -
Journal of Crohn's & Colitis Jan 2022Whereas the exact aetiology of microscopic colitis [MC] remains unknown, a dysregulated immune response to luminal factors or medications is the most accepted...
BACKGROUND
Whereas the exact aetiology of microscopic colitis [MC] remains unknown, a dysregulated immune response to luminal factors or medications is the most accepted pathogenesis hypothesis.
METHODS
We conducted a systematic review of the pathogenesis of MC. We applied the Joanna Briggs Institute methodologies and the PRISMA statement for the reporting of systematic reviews [PROSPERO Trial Identifier: CRD42020145008]. Populations, Exposure of interest, and Outcome [PEO] questions were used to explore the following topics in MC: 1] intestinal luminal factors; 2] autoimmunity; 3] innate immunity; 4] adaptive immunity; 5] extracellular matrix; 6] genetic risk factors; and 7] mechanism of diarrhoea. A search was done in PubMed, Embase, and Web of Science up to February 2020. A narrative description was performed explaining the findings for each aspect of MC aetiopathogenesis.
RESULTS
Thirty-eight documents provided evidence for PEO1, 100 for PEO2, 72 for PEO3 and 4, 38 for PEO5, 20 for PEO6, and 23 for PEO7. The majority of documents were cohorts, case reports, and case series, with a few case-control and some experimental studies. Consistency among data provided by different studies was considered to support pathogenetic hypotheses. MC is a multifactorial disease believed to involve innate and adaptive immune responses to luminal factors, genetic risk, autoimmunity, and extracellular matrix alterations, all contributing by varied mechanisms to watery diarrhoea.
CONCLUSIONS
This is the first systematic review on the aetiology of MC supporting the notion that MC is a multifactorial disease. However, high-profile studies are lacking, and most evidence derives from small heterogeneous studies.
Topics: Colitis, Microscopic; Humans; Risk Factors
PubMed: 34272945
DOI: 10.1093/ecco-jcc/jjab123 -
Environmental Research May 2021Air pollution is a major public health threat. The present study is the first systematic review (SR) to determine the association of exposure to air pollution and... (Review)
Review
Air pollution is a major public health threat. The present study is the first systematic review (SR) to determine the association of exposure to air pollution and Multiple Sclerosis (MS) Progression. A Literature search was carried out using relevant keywords within several international databases. A comprehensive literature search was carried out systematically and yielded 24 eligible studies concerning the relationship of exposure to air pollution including criteria air pollutants such as particulate matter, NOx and SOx, CO, traffic noise, etc. and MS disease. The results of the included studies reveal that there was a significant relationship between exposure to air pollution and MS development and progression. Although the effect of air pollution in the pathogenesis of MS is notfully known, according to the results of the included studies exposure to polluted air can stimulate several mechanisms that act as risk factors for developing MS and for having disease relapses or neurological disability. The major potential mechanism is Dysimmune inflammatory responses subsequent oxidative stress (OS), which leads to neuroinflammation and breakdown of the normal balance between immunity and self-tolerance. Air pollutants induce and sustain chemical reactions that produce reactive oxygen species (ROSs) and nitrogen reactive species (RNSs) which can initiate inflammatory cascades via the redox-sensitive mitogen-activated protein kinase (MAPK) and NF-κB that recruit and activate neutrophils, monocytes, and dendritic cells that stimulate the adaptive immune responses such as Th1 and Th17 inflammatory responses. The uncontrolled inflammatory responses following these events cause cell death and the release of self-antigens capable of stimulating the production of auto-aggressive T-cells via enhancing antigen presentation and facilitate entry of these cells to the central nervous system. Thus, oxidative stress is the culprit in the systemic inflammation and immune imbalance development and progression, powerful risk factors in MS.
Topics: Air Pollutants; Air Pollution; Central Nervous System; Environmental Exposure; Humans; Multiple Sclerosis; Particulate Matter
PubMed: 33129851
DOI: 10.1016/j.envres.2020.110386