scholarly journals JMJ14 encoded H3K4 demethylase modulates immune responses by regulating defence gene expression and pipecolic acid levels

2019 ◽  
Vol 225 (5) ◽  
pp. 2108-2121 ◽  
Author(s):  
Dan Li ◽  
Ruiying Liu ◽  
Deepjyoti Singh ◽  
Xinyu Yuan ◽  
Pradeep Kachroo ◽  
...  
Keyword(s):  
Gene Expression ◽  
Immune Responses ◽  
Pipecolic Acid ◽  
Defence Gene Expression

Nanoparticle-plasma Membrane Interactions: Thermodynamics, Toxicity and Cellular Response

2020 ◽  
Vol 27 (20) ◽  
pp. 3330-3345
Author(s):  
Ana G. Rodríguez-Hernández ◽  
Rafael Vazquez-Duhalt ◽  
Alejandro Huerta-Saquero
Keyword(s):  
Gene Expression ◽  
Immune Responses ◽  
Cellular Response ◽  
Cellular Level ◽  
Membrane Interactions ◽  
Daily Lives ◽  
Cellular Physiology ◽  
Associated Proteins ◽  
First Contact ◽  
Insight Into

Nanomaterials have become part of our daily lives, particularly nanoparticles contained in food, water, cosmetics, additives and textiles. Nanoparticles interact with organisms at the cellular level. The cell membrane is the first protective barrier against the potential toxic effect of nanoparticles. This first contact, including the interaction between the cell membranes -and associated proteins- and the nanoparticles is critically reviewed here. Nanoparticles, depending on their toxicity, can cause cellular physiology alterations, such as a disruption in cell signaling or changes in gene expression and they can trigger immune responses and even apoptosis. Additionally, the fundamental thermodynamics behind the nanoparticle-membrane and nanoparticle-proteins-membrane interactions are discussed. The analysis is intended to increase our insight into the mechanisms involved in these interactions. Finally, consequences are reviewed and discussed.

scholarly journals Intergenic region 3 of modified vaccinia ankara is a functional site for insert gene expression and allows for potent antigen-specific immune responses

Virology ◽  
2010 ◽  
Vol 403 (2) ◽  
pp. 155-162 ◽  
Author(s):  
Edwin R. Manuel ◽  
Zhongde Wang ◽  
Zhongqi Li ◽  
Corinna La Rosa ◽  
Wendi Zhou ◽  
...  
Keyword(s):  
Gene Expression ◽  
Immune Responses ◽  
Intergenic Region ◽  
Functional Site

scholarly journals Proteomic analyses of defence gene expression in a model tomato‐Verticillium pathosystem

2009 ◽  
Vol 23 (S1) ◽  
Author(s):  
Jane Robb ◽  
Barbara Lee ◽  
Alex Kurosky ◽  
Ross N. Nazar
Keyword(s):  
Gene Expression ◽  
Defence Gene Expression ◽  
Proteomic Analyses

scholarly journals Cellular FLIP Inhibits β-Catenin Ubiquitylation and Enhances Wnt Signaling

2004 ◽  
Vol 24 (19) ◽  
pp. 8418-8427 ◽  
Author(s):  
Mikihiko Naito ◽  
Ryohei Katayama ◽  
Toshiyasu Ishioka ◽  
Akiko Suga ◽  
Kohei Takubo ◽  
...  
Keyword(s):  
Gene Expression ◽  
Immune Responses ◽  
Wnt Signaling ◽  
Axis Formation ◽  
Caspase Activity ◽  
Additional Mechanism ◽  
Long Form ◽  
Fas Signaling ◽  
Canonical Wnt ◽  
Cellular Flip

ABSTRACT Cellular FLIP (cFLIP) is a close homologue of caspase 8 without caspase activity that inhibits Fas signaling. The cFLIP protein is often expressed in human tumors and is believed to suppress antitumor immune responses involving the Fas system. Here, we report that a long form of cFLIP (cFLIP-L) inhibits β-catenin ubiquitylation and increases endogenous cytosolic β-catenin, which results in translocation of β-catenin into nuclei and induction of β-catenin-dependent gene expression in cFLIP-L-expressing cells. When cells stably expressing cFLIP-L were stimulated with Wnt3a, enhanced Wnt signaling was observed compared with the control cells. Conversely, depletion of endogenous cFLIP results in reduced Wnt signaling. Furthermore, cFLIP-L increases secondary-body axis formation when coinjected with suboptimal doses of β-catenin into early Xenopus embryos. Down-regulation of FADD by RNA-mediated interference abolishes the β-catenin-dependent gene expression induced by cFLIP-L. These results indicate that cFLIP-L, in cooperation with FADD, enhances canonical Wnt signaling by inhibiting proteasomal degradation of β-catenin, thus suggesting an additional mechanism involved with tumorgenesis, in addition to inhibiting Fas signaling.

scholarly journals Integrative Transcriptomics Reveals Activation of Innate Immune Responses and Inhibition of Inflammation During Oral Immunotherapy for Egg Allergy in Children

2021 ◽  
Vol 12 ◽  
Author(s):  
Piia Karisola ◽  
Kati Palosuo ◽  
Victoria Hinkkanen ◽  
Lukas Wisgrill ◽  
Terhi Savinko ◽  
...  
Keyword(s):  
Gene Expression ◽  
Clinical Outcome ◽  
Immune Responses ◽  
Molecular Mechanisms ◽  
Expression Patterns ◽  
Oral Immunotherapy ◽  
Innate Immune ◽  
Egg Allergy ◽  
Innate Immune Responses ◽  
Open Label

We previously reported the results of a randomized, open-label trial of egg oral immunotherapy (OIT) in 50 children where 44% were desensitized and 46% were partially desensitized after 8 months of treatment. Here we focus on cell-mediated molecular mechanisms driving desensitization during egg OIT. We sought to determine whether changes in genome-wide gene expression in blood cells during egg OIT correlate with humoral responses and the clinical outcome. The blood cell transcriptome of 50 children receiving egg OIT was profiled using peripheral blood mononuclear cell (PBMC) samples obtained at baseline and after 3 and 8 months of OIT. We identified 467 differentially expressed genes (DEGs) after 3 or 8 months of egg OIT. At 8 months, 86% of the DEGs were downregulated and played a role in the signaling of TREM1, IL-6, and IL-17. In correlation analyses, Gal d 1–4-specific IgG4 antibodies associated positively with DEGs playing a role in pathogen recognition and antigen presentation and negatively with DEGs playing a role in the signaling of IL-10, IL-6, and IL-17. Desensitized and partially desensitized patients had differences in their antibody responses, and although most of the transcriptomic changes were shared, both groups had also specific patterns, which suggest slower changes in partially desensitized and activation of NK cells in the desensitized group. OIT for egg allergy in children inhibits inflammation and activates innate immune responses regardless of the clinical outcome at 8 months. Changes in gene expression patterns first appear as posttranslational protein modifications, followed by more sustained epigenetic gene regulatory functions related to successful desensitization.

scholarly journals P014 Identification of Crohn’s disease immunopathotypes

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S137-S137
Author(s):  
H M Baer ◽  
E MacDonald ◽  
A Ferguson ◽  
A M Scott ◽  
M I Khan ◽  
...  
Keyword(s):  
Gene Expression ◽  
Immune Response ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Immune Responses ◽  
Mononuclear Cells ◽  
Local Immune Response ◽  
Cross Sectional ◽  
Treatment Responses ◽  
Colonic Biopsies

Abstract Background Crohn’s disease (CD) is a chronic inflammatory gastrointestinal condition, with globally increasing incidence. Patients with CD suffer from a loss of tolerance towards their commensal microbiota causing an aberrant immune response, occurring in a protracted relapse and remission cycle. Although a variety of frontline therapies is currently available, including targeted therapies such as biologic drugs, 30–40% of CD patients still require surgery to manage the disease. At present, the immunobiology of CD is not fully understood. However, differences in immune responses between patients might play an important role in diverse treatment responses. The aim of this study was to identify differences in peripheral and local immune responses of CD to understand differences in disease behaviour and treatment outcome. Methods Peripheral blood mononuclear cells and plasma were isolated from whole blood of a cross-sectional CD patient cohort (nCD = 12) and normal controls (NC, nNC = 28). Flow cytometry analysis and multiplex assays were used to quantify immune cell populations and cytokine levels, respectively. The local immune response was analysed by bulk RNA sequencing of mucosal colonic biopsies either from inflamed CD or normal tissue. Gene signatures were then followed up by validation in publicly deposited gene expression datasets (nCD = 36, nNC = 24), and by measurement of specific proteins using our archived samples. Results Peripheral immunophenotyping of the initial cross-sectional study displayed three different types of CD patients, characterised by either a decrease in leukocyte populations, an increase of cytokines, or a change in both. Analysis of the RNAseq data derived from colonic biopsies revealed four distinct clusters in genes associated with the immune response in CD patients. Further pathway analysis showed one cluster with an enriched B cell signature and another cluster with an elevated macrophage and neutrophil response. We utilised publicly available gene expression datasets to validate these signatures in a larger cohort and identified a selection of patients with an up-regulated pro-inflammatory macrophage response. Using correlation analysis, we suggest an immunopathotype with increased macrophage activation which is potentially associated with a more severe form of the disease. Conclusion We have identified distinct immunopathotypes in both the peripheral and local immune response of CD patients. Further investigation will correlate these distinct immune responses in CD with clinical parameters, to understand associations between diverse treatment responses and disease behaviours.

scholarly journals Systems Vaccinology for a Live Attenuated Tularemia Vaccine Reveals Unique Transcriptional Signatures That Predict Humoral and Cellular Immune Responses

Vaccines ◽  
2019 ◽  
Vol 8 (1) ◽  
pp. 4 ◽  
Author(s):  
Muktha S. Natrajan ◽  
Nadine Rouphael ◽  
Lilin Lai ◽  
Dmitri Kazmin ◽  
Travis L. Jensen ◽  
...  
Keyword(s):  
Gene Expression ◽  
T Cell ◽  
Immune Responses ◽  
T Cell Responses ◽  
Innate Immune ◽  
Antibody Responses ◽  
Cytokine Signaling ◽  
Cell Responses ◽  
Viral Vaccine ◽  
Tularemia Vaccine

Background: Tularemia is a potential biological weapon due to its high infectivity and ease of dissemination. This study aimed to characterize the innate and adaptive responses induced by two different lots of a live attenuated tularemia vaccine and compare them to other well-characterized viral vaccine immune responses. Methods: Microarray analyses were performed on human peripheral blood mononuclear cells (PBMCs) to determine changes in transcriptional activity that correlated with changes detected by cellular phenotyping, cytokine signaling, and serological assays. Transcriptional profiles after tularemia vaccination were compared with yellow fever [YF-17D], inactivated [TIV], and live attenuated [LAIV] influenza. Results: Tularemia vaccine lots produced strong innate immune responses by Day 2 after vaccination, with an increase in monocytes, NK cells, and cytokine signaling. T cell responses peaked at Day 14. Changes in gene expression, including upregulation of STAT1, GBP1, and IFIT2, predicted tularemia-specific antibody responses. Changes in CCL20 expression positively correlated with peak CD8+ T cell responses, but negatively correlated with peak CD4+ T cell activation. Tularemia vaccines elicited gene expression signatures similar to other replicating vaccines, inducing early upregulation of interferon-inducible genes. Conclusions: A systems vaccinology approach identified that tularemia vaccines induce a strong innate immune response early after vaccination, similar to the response seen after well-studied viral vaccines, and produce unique transcriptional signatures that are strongly correlated to the induction of T cell and antibody responses.

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