scholarly journals Ion channels and anti-cancer immunity

2014 ◽  
Vol 369 (1638) ◽  
pp. 20130106 ◽  
Author(s):  
Gyorgy Panyi ◽  
Christine Beeton ◽  
Antonio Felipe
Keyword(s):  
Ion Channels ◽  
Immune Cell ◽  
Specific Antigen ◽  
Cell Subset ◽  
Cell Types ◽  
Cancer Tissue ◽  
Specific Expression ◽  
Cancer Disease ◽  
And Function ◽  
Key Steps

The outcome of a malignant disease depends on the efficacy of the immune system to destroy cancer cells. Key steps in this process, for example the generation of a proper Ca 2+ signal induced by recognition of a specific antigen, are regulated by various ion channel including voltage-gated Kv1.3 and Ca 2+ -activated KCa3.1 K + channels, and the interplay between Orai and STIM to produce the Ca 2+ -release-activated Ca 2+ (CRAC) current required for T-cell proliferation and function. Understanding the immune cell subset-specific expression of ion channels along with their particular function in a given cell type, and the role of cancer tissue-dependent factors in the regulation of operation of these ion channels are emerging questions to be addressed in the fight against cancer disease. Answering these questions might lead to a better understanding of the immunosuppression phenomenon in cancer tissue and the development of drugs aimed at skewing the distribution of immune cell types towards killing of the tumour cells.

scholarly journals Single cell analysis reveals immune cell–adipocyte crosstalk regulating the transcription of thermogenic adipocytes

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Prashant Rajbhandari ◽  
Douglas Arneson ◽  
Sydney K Hart ◽  
In Sook Ahn ◽  
Graciel Diamante ◽  
...  
Keyword(s):  
Single Cell ◽  
Immune Cells ◽  
Immune Cell ◽  
Single Cell Analysis ◽  
Metabolic Response ◽  
Cell Types ◽  
Specific Cell ◽  
Beneficial Effects ◽  
Thermogenic Adipocytes ◽  
And Function

Immune cells are vital constituents of the adipose microenvironment that influence both local and systemic lipid metabolism. Mice lacking IL10 have enhanced thermogenesis, but the roles of specific cell types in the metabolic response to IL10 remain to be defined. We demonstrate here that selective loss of IL10 receptor α in adipocytes recapitulates the beneficial effects of global IL10 deletion, and that local crosstalk between IL10-producing immune cells and adipocytes is a determinant of thermogenesis and systemic energy balance. Single Nuclei Adipocyte RNA-sequencing (SNAP-seq) of subcutaneous adipose tissue defined a metabolically-active mature adipocyte subtype characterized by robust expression of genes involved in thermogenesis whose transcriptome was selectively responsive to IL10Rα deletion. Furthermore, single-cell transcriptomic analysis of adipose stromal populations identified lymphocytes as a key source of IL10 production in response to thermogenic stimuli. These findings implicate adaptive immune cell-adipocyte communication in the maintenance of adipose subtype identity and function.

scholarly journals Sex differences in autoimmunity could be associated with altered regulatory T cell phenotype and lipoprotein metabolism

2019 ◽  
Author(s):  
George A Robinson ◽  
Kirsty E Waddington ◽  
Marsilio Adriani ◽  
Anna Radziszewska ◽  
Hannah Peckham ◽  
...  
Keyword(s):  
Sex Differences ◽  
T Cell ◽  
Regulatory T Cell ◽  
Immune Cell ◽  
Pubertal Development ◽  
Cell Subset ◽  
Cell Phenotype ◽  
Healthy Adolescent ◽  
Treg Frequency ◽  
And Function

ABSTRACTMale and female immune responses are known to differ resulting in an increased prevalence of autoimmunity in women. Here sex differences in T-cell subset frequency and function during adolescence were examined in healthy donors and patients with the autoimmune disease juvenile (J)SLE; onset of JSLE commonly occurs during puberty suggesting a strong hormonal influence. Healthy adolescent males had increased regulatory T-cell (Treg) frequency, and increased Treg suppressive capacity and IL-4 production compared to healthy adolescent females. The T-helper 2-like profile in male Tregs was associated with increased expression of GATA3 which correlated significantly with elevated Treg plasma membrane glycosphingolipid expression. Differential Treg phenotype was associated with unique serum metabolomic profiles in males compared to female adolescents. Notably, very low density lipoprotein (VLDL) metabolomic signatures correlated positively with activated Tregs in males but with resting Tregs in females. Consistently, only VLDL isolated from male serum was able to induce increased Treg IL-4 production and glycosphingolipid expression following in cultured cells. Remarkably, gender differences in Treg frequency, phenotype and function and serum metabolomic profiles were lost in adolescents with JSLE. This work provides evidence that a combination of pubertal development, immune cell defects and dyslipidemia may contribute to JSLE pathogenesis.

scholarly journals Nonneuronal Cholinergic System in Breast Tumors and Dendritic Cells: Does It Improve or Worsen the Response to Tumor?

2013 ◽  
Vol 2013 ◽  
pp. 1-12
Author(s):  
Marisa Vulcano ◽  
María Gabriela Lombardi ◽  
María Elena Sales
Keyword(s):  
Dendritic Cells ◽  
Cholinergic System ◽  
Parasympathetic Nervous System ◽  
Immune Cell ◽  
Breast Tumors ◽  
Cell Types ◽  
Cellular Functions ◽  
And Migration ◽  
And Function

Besides being the main neurotransmitter in the parasympathetic nervous system, acetylcholine (ACh) can act as a signaling molecule in nonneuronal tissues. For this reason, ACh and the enzymes that synthesize and degrade it (choline acetyltransferase and acetylcholinesterase) as well as muscarinic (mAChRs) and nicotinic receptors conform the non-neuronal cholinergic system (nNCS). It has been reported that nNCS regulates basal cellular functions including survival, proliferation, adhesion, and migration. Moreover, nNCS is broadly expressed in tumors and in different components of the immune system. In this review, we summarize the role of nNCS in tumors and in different immune cell types focusing on the expression and function of mAChRs in breast tumors and dendritic cells (DCs) and discussing the role of DCs in breast cancer.

scholarly journals Breakdown of multiple sclerosis genetics to identify an integrated disease network and potential variant mechanisms

2019 ◽  
Vol 51 (11) ◽  
pp. 562-577
Author(s):  
C. Joy Shepard ◽  
Sara G. Cline ◽  
David Hinds ◽  
Seyedehameneh Jahanbakhsh ◽  
Jeremy W. Prokop
Keyword(s):  
Multiple Sclerosis ◽  
Immune Cell ◽  
Expression Profiles ◽  
Missense Variant ◽  
Cell Types ◽  
Tissue Expression ◽  
Specific Expression ◽  
Genomic Databases ◽  
Genetic Traits ◽  
Immune System Dysfunction

Genetics of multiple sclerosis (MS) are highly polygenic with few insights into mechanistic associations with pathology. In this study, we assessed MS genetics through linkage disequilibrium and missense variant interpretation to yield a MS gene network. This network of 96 genes was taken through pathway analysis, tissue expression profiles, single cell expression segregation, expression quantitative trait loci (eQTLs), genome annotations, transcription factor (TF) binding profiles, structural genome looping, and overlap with additional associated genetic traits. This work revealed immune system dysfunction, nerve cell myelination, energetic control, transcriptional regulation, and variants that overlap multiple autoimmune disorders. Tissue-specific expression and eQTLs of MS genes implicate multiple immune cell types including macrophages, neutrophils, and T cells, while the genes in neural cell types enrich for oligodendrocyte and myelin sheath biology. There are eQTLs in linkage with lead MS variants in 25 genes including the multitissue eQTL, rs9271640, for HLA-DRB1/ DRB5. Using multiple functional genomic databases, we identified noncoding variants that disrupt TF binding for GABPA, CTCF, EGR1, YY1, SPI1, CLOCK, ARNTL, BACH1, and GFI1. Overall, this paper suggests multiple genetic mechanisms for MS associated variants while highlighting the importance of a systems biology and network approach when elucidating intersections of the immune and nervous system.

scholarly journals Long Noncoding RNA in Myeloid and Lymphoid Cell Differentiation, Polarization and Function

Cells ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 269 ◽  
Author(s):  
Imran Ahmad ◽  
Araceli Valverde ◽  
Fayek Ahmad ◽  
Afsar Raza Naqvi
Keyword(s):  
Cell Differentiation ◽  
Immune Cells ◽  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Immune Cell ◽  
Lymphoid Cells ◽  
Tissue Cell ◽  
Specific Expression ◽  
And Function

Long noncoding RNA (lncRNA) are a class of endogenous, non-protein coding RNAs that are increasingly being associated with various cellular functions and diseases. Yet, despite their ubiquity and abundance, only a minute fraction of these molecules has an assigned function. LncRNAs show tissue-, cell-, and developmental stage-specific expression, and are differentially expressed under physiological or pathological conditions. The role of lncRNAs in the lineage commitment of immune cells and shaping immune responses is becoming evident. Myeloid cells and lymphoid cells are two major classes of immune systems that work in concert to initiate and amplify innate and adaptive immunity in vertebrates. In this review, we provide mechanistic roles of lncRNA through which these noncoding RNAs can directly participate in the differentiation, polarization, and activation of myeloid (monocyte, macrophage, and dendritic cells) and lymphoid cells (T cells, B cells, and NK cells). While our knowledge on the role of lncRNA in immune cell differentiation and function has improved in the past decade, further studies are required to unravel the biological role of lncRNAs and identify novel mechanisms of lncRNA functions in immune cells. Harnessing the regulatory potential of lncRNAs can provide novel diagnostic and therapeutic targets in treating immune cell related diseases.

scholarly journals Hypoxia. 4. Hypoxia and ion channel function

2011 ◽  
Vol 300 (5) ◽  
pp. C951-C967 ◽  
Author(s):  
Larissa A. Shimoda ◽  
Jan Polak
Keyword(s):  
Ion Channels ◽  
Cell Function ◽  
Critical Role ◽  
Cardiac Contractility ◽  
Cell Types ◽  
Cellular Processes ◽  
Oxygen Sensitive ◽  
Sense And Respond ◽  
And Function ◽  
And Control

The ability to sense and respond to oxygen deprivation is required for survival; thus, understanding the mechanisms by which changes in oxygen are linked to cell viability and function is of great importance. Ion channels play a critical role in regulating cell function in a wide variety of biological processes, including neuronal transmission, control of ventilation, cardiac contractility, and control of vasomotor tone. Since the 1988 discovery of oxygen-sensitive potassium channels in chemoreceptors, the effect of hypoxia on an assortment of ion channels has been studied in an array of cell types. In this review, we describe the effects of both acute and sustained hypoxia (continuous and intermittent) on mammalian ion channels in several tissues, the mode of action, and their contribution to diverse cellular processes.

scholarly journals Adeno-Associated Virus Technologies and Methods for Targeted Neuronal Manipulation

2019 ◽  
Author(s):  
Leila Haery ◽  
Benjamin E. Deverman ◽  
Katherine Matho ◽  
Ali Cetin ◽  
Kenton Woodard ◽  
...  
Keyword(s):  
Viral Vectors ◽  
Cell Types ◽  
Regulatory Elements ◽  
Specific Cell ◽  
Specific Expression ◽  
Adeno Associated Virus ◽  
Cell Type Specific Expression ◽  
Cell Type Specific ◽  
And Function ◽  
Novel Applications

AbstractCell-type-specific expression of molecular tools and sensors is critical to construct circuit diagrams and to investigate the activity and function of neurons within the nervous system. Strategies for targeted manipulation include combinations of classical genetic tools such as Cre/loxP and Flp/FRT, use of cis-regulatory elements, targeted knock-in transgenic mice, and gene delivery by AAV and other viral vectors. The combination of these complex technologies with the goal of precise neuronal targeting is a challenge in the lab. This report will discuss the theoretical and practical aspects of combining current technologies and establish best practices for achieving targeted manipulation of specific cell types. Novel applications and tools, as well as areas for development, will be envisioned and discussed.

scholarly journals Multi-Omic Analyses of the m5C Regulator ALYREF Reveal Its Essential Roles in Hepatocellular Carcinoma

2021 ◽  
Vol 11 ◽  
Author(s):  
Chen Xue ◽  
Yalei Zhao ◽  
Ganglei Li ◽  
Lanjuan Li
Keyword(s):  
Gene Expression ◽  
Hepatocellular Carcinoma ◽  
Immune Cell ◽  
The Cancer Genome Atlas ◽  
Cancer Tissue ◽  
Hub Genes ◽  
Specific Expression ◽  
Tissue Samples ◽  
Expression Levels ◽  
Advanced Tumor

The ALYREF protein acts as a crucial epigenetic regulator in several cancers. However, the specific expression levels and functional roles of ALYREF in cancers are largely unknown, including for hepatocellular carcinoma (HCC). In a pan-cancer tissue analysis that included HCC, we assessed the expression of ALYREF compared to normal tissues using The Cancer Genome Atlas database. Associations between ALYREF gene expression and the clinical characteristics of HCC patient samples were assessed using the UALCAN database. Kaplan-Meier plots were performed to assess HCC patient prognosis, and the TIMER database was used to explore associations between ALYREF expression and immune-cell infiltrations. The same methods were used to assess eIF4A3 expression in HCC patient samples. In addition, ALYREF- and elF4A3-related differentially expressed genes (DEGs) were determined using LinkedOmics, associated protein functionalities were predicted for positively associated DEGs, and both the TargetScan and miRDB databases were used to predict potential upstream miRNAs for control of ALYREF and eIF4A3 expression. We found that ALYREF gene expression was dysregulated in several cancers and was significantly elevated in HCC patient tissue samples and HCC cell lines. The overexpression of ALYREF was significantly related to both advanced tumor-node-metastasis stages and poor HCC prognosis. Furthermore, we found that eIF4A3 expression was significantly correlated with ALYREF expression, and that upregulated eIF4A3 was significantly associated with poor HCC patient outcomes. In the protein-protein interaction network, we identified eight hub genes based on the positively associated DEGs in common between ALYREF and eIF4A3, and the high expression levels of these hub genes were positively associated with patient clinical outcomes. In addition, we identified miR-4666a-5p and miR-6124 as potential regulators of ALYREF and eIF4A3 expression. These findings suggest that increased ALYREF expression may function as a novel biomarker for both HCC diagnosis and prognosis predictions.

scholarly journals Notch–RBP-J signaling controls the homeostasis of CD8− dendritic cells in the spleen

2007 ◽  
Vol 204 (7) ◽  
pp. 1653-1664 ◽  
Author(s):  
Michele L. Caton ◽  
Matthew R. Smith-Raska ◽  
Boris Reizis
Keyword(s):  
Target Gene ◽  
Immune Cell ◽  
Notch Pathway ◽  
Cell Types ◽  
Innate Immune ◽  
Receptor Ligands ◽  
Notch Receptors ◽  
And Function

Signaling through Notch receptors and their transcriptional effector RBP-J is essential for lymphocyte development and function, whereas its role in other immune cell types is unclear. We tested the function of the canonical Notch–RBP-J pathway in dendritic cell (DC) development and maintenance in vivo. Genetic inactivation of RBP-J in the bone marrow did not preclude DC lineage commitment but caused the reduction of splenic DC fraction. The inactivation of RBP-J in DCs using a novel DC-specific deleter strain caused selective loss of the splenic CD8− DC subset and reduced the frequency of cytokine-secreting CD8− DCs after challenge with Toll-like receptor ligands. In contrast, other splenic DC subsets and DCs in the lymph nodes and tissues were unaffected. The RBP-J–deficient splenic CD8− DCs were depleted at the postprogenitor stage, exhibited increased apoptosis, and lost the expression of the Notch target gene Deltex1. In the spleen, CD8− DCs were found adjacent to cells expressing the Notch ligand Delta-like 1 in the marginal zone (MZ). Thus, canonical Notch–RBP-J signaling controls the maintenance of CD8− DCs in the splenic MZ, revealing an unexpected role of the Notch pathway in the innate immune system.

scholarly journals Is zebrafish heart regeneration “complete”? Lineage-restricted cardiomyocytes proliferate to pre-injury numbers but some fail to differentiate in fibrotic hearts

2020 ◽  
Author(s):  
Alberto Bertozzi ◽  
Chi-Chung Wu ◽  
Phong D. Nguyen ◽  
Mohankrishna Dalvoy Vasudevarao ◽  
Medhanie A. Mulaw ◽  
...  
Keyword(s):  
Immune Cell ◽  
Cell Types ◽  
Scar Tissue ◽  
Lineage Tracing ◽  
Cardiomyocyte Differentiation ◽  
Cardiomyocyte Proliferation ◽  
Quantitative Evidence ◽  
Cell Lineages ◽  
And Function ◽  
Zebrafish Heart

AbstractAdult zebrafish are frequently described to be able to “completely” regenerate the heart. Yet, the extent to which cardiomyocytes lost to injury are replaced is unknown, since only indirect or non-quantitative evidence for cardiomyocyte proliferation exists. We established stereological methods to quantify the number of cardiomyocytes at several time-points post cryoinjury. Intriguingly, after cryoinjuries that killed about 1/3 of the ventricular cardiomyocytes, pre-injury cardiomyocyte numbers were restored already within 30 days. Yet, many hearts retained small residual scars, and a subset of cardiomyocytes bordering these fibrotic areas remained smaller, lacked differentiated sarcomeric structures, and displayed defective calcium signaling. Thus, a subset of regenerated cardiomyocytes failed to fully mature. While lineage-tracing experiments have shown that regenerating cardiomyocytes are derived from differentiated cardiomyocytes, technical limitations have previously made it impossible to test whether cardiomyocyte trans-differentiation contributes to regeneration of non-myocyte cell lineages. Using Cre responder lines that are expressed in all major cell types of the heart, we found no evidence for cardiomyocyte transdifferentiation into endothelial, epicardial, fibroblast or immune cell lineages. Overall, our results imply a refined answer to the question whether zebrafish can completely regenerate the heart: in response to cryoinjury, preinjury cardiomyocyte numbers are indeed completely regenerated, while restoration of cardiomyocyte differentiation and function, as well as resorption of scar tissue, is less robustly achieved.

Sign in / Sign up

Export Citation Format

Share Document