IgA deficiency destabilizes homeostasis toward intestinal microbes and increases systemic immune dysregulation DOI
Peyton Conrey, Lidiya Denu, Kaitlin C. O’Boyle

et al.

Science Immunology, Journal Year: 2023, Volume and Issue: 8(83)

Published: May 26, 2023

The ability of most patients with selective immunoglobulin A (IgA) deficiency (SIgAD) to remain apparently healthy has been a persistent clinical conundrum. Compensatory mechanisms, including IgM, have proposed, yet it remains unclear how secretory IgA and IgM work together in the mucosal system and, on larger scale, whether systemic anti-commensal responses are redundant or unique features. To address this gap knowledge, we developed an integrated host-commensal approach combining microbial flow cytometry metagenomic sequencing (mFLOW-Seq) comprehensively define which microbes induce antibodies. We coupled high-dimensional immune profiling study cohort pediatric SIgAD household control siblings. found that antibody networks cooperate maintain homeostasis by targeting common subset commensal microbes. In IgA-deficiency, find increased translocation specific bacterial taxa associated elevated levels IgG fecal microbiota. Associated features dysregulation IgA-deficient mice humans included inflammatory cytokines, enhanced follicular CD4 T helper cell frequency activation, altered CD8 activation state. Although is clinically defined absence serum IgA, symptomatology were concentrated participants who also deficient. These findings reveal leads aberrant exposures microbes, increase likelihood humoral cellular symptomatic disease deficiency.

Language: Английский

Nanoparticles and innate immunity: new perspectives on host defence DOI
Diana Boraschi, Paola Italiani, Roberto Palomba

et al.

Seminars in Immunology, Journal Year: 2017, Volume and Issue: 34, P. 33 - 51

Published: Aug. 31, 2017

Language: Английский

Citations

290
<p>Immunoinformatics and Vaccine Development: An Overview</p> DOI Creative Commons
Angus Nnamdi Oli,

Wilson Okechukwu Obialor,

M Ifeanyichukwu

et al.

ImmunoTargets and Therapy, Journal Year: 2020, Volume and Issue: Volume 9, P. 13 - 30

Published: Feb. 1, 2020

Abstract: The use of vaccines have resulted in a remarkable improvement global health. It has saved several lives, reduced treatment costs and raised the quality animal human lives. Current traditional came empirically with either vague or completely no knowledge how they modulate our immune system. Even at face potential vaccine design advance, immune-related concerns (as seen specific vulnerable populations, cases emerging/re-emerging infectious disease, pathogens complex lifecycle antigenic variability, need for personalized vaccinations, vaccines' immunological safety -specifically likelihood to trigger non-antigen-specific responses that may cause autoimmunity allergy) are being raised. And these driven immunologists toward research better approach will consider challenges. Currently, immunoinformatics paved way understanding some disease pathogenesis, diagnosis, system response computational vaccinology. importance this study diseases is diverse terms approaches used, but united by common qualities related host–pathogen relationship. Bioinformatics methods also used assign functions uncharacterized genes which can be targeted as candidate inclusion women pregnant into trials programs. essence review give insight focus on novel computational, experimental computation-driven studying interactions thus making case its development. Keywords: immunoinformatics, vaccinology, design, emerging infections, system; vaccinology

Language: Английский

Citations

211
Distinctive roles of age, sex, and genetics in shaping transcriptional variation of human immune responses to microbial challenges DOI Creative Commons

Barbara Piasecka,

Darragh Duffy, Alejandra Urrutia

et al.

Proceedings of the National Academy of Sciences, Journal Year: 2017, Volume and Issue: 115(3)

Published: Dec. 27, 2017

Significance Identifying the drivers of interindividual diversity human immune system is crucial to understand their consequences on immune-mediated diseases. By examining transcriptional responses 1,000 individuals various microbial challenges, we show that age and sex influence expression many immune-related genes, but effects are overall moderate, whereas genetic factors affect a smaller gene set with stronger effect. We identify numerous variants variation infection, which associated autoimmune or inflammatory disorders. These results enable additional exploration role regulatory in pathogenesis diseases improve our understanding respective age, sex, genetics response variation.

Language: Английский

Citations

205
Systems-Level Immunomonitoring from Acute to Recovery Phase of Severe COVID-19 DOI Creative Commons
Lucie Rodriguez, Pirkka T. Pekkarinen, Tadepally Lakshmikanth

et al.

Cell Reports Medicine, Journal Year: 2020, Volume and Issue: 1(5), P. 100078 - 100078

Published: Aug. 1, 2020

HighlightsImmunomonitoring from acute to recovery phase COVID-19An IFNγ-eosinophil axis precedes lung hyperinflammationBasophils modulate SARS-CoV-2 IgG responsesA shared trajectory of immunological in COVID-19SummarySevere disease is characterized by vigorous inflammatory responses the lung, often with a sudden onset after 5–7 days stable disease. Efforts this hyperinflammation and associated respiratory distress syndrome rely on unraveling immune cell interactions cytokines that drive such responses. Given every patient captured at different stages infection, longitudinal monitoring response critical systems-level analyses are required capture cellular interactions. Here, we report blood immunomonitoring study 37 adult patients diagnosed COVID-19 followed up 14 samples phases We describe an activated before changes cell-cell co-regulation during also map among severe COVID-19.Graphical abstract

Language: Английский

Citations

198
Organ‐on‐a‐Chip for Cancer and Immune Organs Modeling DOI
Wujin Sun, Zhimin Luo, Junmin Lee

et al.

Advanced Healthcare Materials, Journal Year: 2019, Volume and Issue: 8(4)

Published: Jan. 3, 2019

Bridging the gap between findings in preclinical 2D cell culture models and vivo tissue cultures has been challenging; simple microenvironment of monolayer systems may not capture cellular response to drugs accurately. Three-dimensional organotypic have gained increasing interest due their ability recreate precise organizations. These facilitate investigation interactions different sub-tissue level components through providing physiologically relevant microenvironments for cells vitro. The incorporation human-sourced tissues into these further enables personalized prediction drug responses. Integration microfluidic units 3D can be used control local environment, dynamic simulation behaviors, real-time readout testing data. Cancer immune system related diseases are severe burdens our health care created an urgent need high-throughput, effective development plans. This review focuses on recent progress "cancer-on-a-chip" "immune organs-on-a-chip" designed study disease progression predict drug-induced Future challenges opportunities also discussed.

Language: Английский

Citations

193
Underlying features of epigenetic aging clocks in vivo and in vitro DOI Creative Commons
Zuyun Liu,

Diana L. Leung,

Kyra Thrush

et al.

Aging Cell, Journal Year: 2020, Volume and Issue: 19(10)

Published: Sept. 15, 2020

Epigenetic clocks, developed using DNA methylation data, have been widely used to quantify biological aging in multiple tissues/cells. However, many existing epigenetic clocks are weakly correlated with each other, suggesting they may capture different processes. We utilize multi-omics data from diverse human tissue/cells identify shared features across eleven clocks. Despite the striking lack of overlap CpGs, analysis suggested five (Horvath1, Horvath2, Levine, Hannum, and Lin) share transcriptional associations conserved purified CD14+ monocytes dorsolateral prefrontal cortex. The pathways enriched association links between metabolism, immunity, autophagy. Results vitro experiments showed that two (Levine were accelerated accordance hallmarks aging-cellular senescence mitochondrial dysfunction. Finally, multi-tissue deconstruct clock signals, we a meta-clock demonstrated improved prediction for mortality robustly related than single

Language: Английский

Citations

184
Genetic regulatory effects modified by immune activation contribute to autoimmune disease associations DOI Creative Commons
Sarah Kim-Hellmuth,

Matthias Bechheim,

Benno Pütz

et al.

Nature Communications, Journal Year: 2017, Volume and Issue: 8(1)

Published: Aug. 8, 2017

The immune system plays a major role in human health and disease, understanding genetic causes of interindividual variability responses is vital. Here, we isolate monocytes from 134 genotyped individuals, stimulate these cells with three defined microbe-associated molecular patterns (LPS, MDP, 5'-ppp-dsRNA), profile the transcriptomes at time points. Mapping expression quantitative trait loci (eQTL), identify 417 response eQTLs (reQTLs) varying effects between conditions. We characterize dynamics regulation on early late observe an enrichment reQTLs distal cis-regulatory elements. In addition, are enriched for recent positive selection evolutionary trend towards enhanced response. Finally, uncover reQTL multiple GWAS show stronger than constant signals several autoimmune diseases. This demonstrates importance infectious stimuli modifying predisposition to disease.Insight into influence important pathologies. authors generate transcriptome data blood stimulated various provide time-resolved eQTL map.

Language: Английский

Citations

181
The potential of hyaluronic acid in immunoprotection and immunomodulation: Chemistry, processing and function DOI Creative Commons
Fernanda Zamboni, Sílvia Vieira, Rui L. Reis

et al.

Progress in Materials Science, Journal Year: 2018, Volume and Issue: 97, P. 97 - 122

Published: April 22, 2018

Language: Английский

Citations

179
Broad immune activation underlies shared set point signatures for vaccine responsiveness in healthy individuals and disease activity in patients with lupus DOI
Yuri Kotliarov, Rachel Sparks, Andrew J. Martins

et al.

Nature Medicine, Journal Year: 2020, Volume and Issue: 26(4), P. 618 - 629

Published: Feb. 24, 2020

Language: Английский

Citations

175
Signatures of CD8+ T cell dysfunction in AML patients and their reversibility with response to chemotherapy DOI Open Access
Hanna A. Knaus, Sofia Berglund, Hubert Hackl

et al.

JCI Insight, Journal Year: 2018, Volume and Issue: 3(21)

Published: Nov. 1, 2018

Our understanding of phenotypic and functional signatures CD8+ T cell dysfunction in acute myeloid leukemia (AML) is limited. Deciphering these deranged states how they are impacted by induction chemotherapy essential for incorporation novel immune-based strategies to restore maintain antileukemia immunity.We utilized high-dimensional immunophenotyping, gene expression, studies characterize peripheral blood bone marrow cells 72 AML patients at diagnosis after chemotherapy.Our data suggest that multiple aspects function operative diagnosis, with exhaustion senescence being the dominant processes. Following treatment, transcriptional profile diverged between responders nonresponders. Response therapy correlated upregulation costimulatory, downregulation apoptotic inhibitory, signaling pathways, indicative restoration function. In studies, blasts directly altered viability, expansion, co-signaling marker expression. This was part reversible upon PD-1 blockade or OX40 costimulation vitro.Our findings highlight uniqueness sculpting responses plasticity their response, providing a compelling rationale integration immunotherapies augment immunity.This work supported Leukemia & Lymphoma Society grant no. 6449-13; NIH grants UM1-CA186691 R01-HL110907-01; American Blood Marrow Transplantation New Investigator Award/Gabrielle's Angel Foundation; Vienna Fund Innovative Cancer Research; fellowships from Wenner-Gren Foundation Swedish Medical Research.

Language: Английский

Citations

171