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Epigenetics immune response

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https://www.readbyqxmd.com/read/28334849/icf-specific-dnmt3b-dysfunction-interferes-with-intragenic-regulation-of-mrna-transcription-and-alternative-splicing
#1
Sole Gatto, Miriam Gagliardi, Monica Franzese, Sylwia Leppert, Mariarosaria Papa, Marco Cammisa, Giacomo Grillo, Guillame Velasco, Claire Francastel, Shir Toubiana, Maurizio D'Esposito, Claudia Angelini, Maria R Matarazzo
Hypomorphic mutations in DNA-methyltransferase DNMT3B cause majority of the rare disorder Immunodeficiency, Centromere instability and Facial anomalies syndrome cases (ICF1). By unspecified mechanisms, mutant-DNMT3B interferes with lymphoid-specific pathways resulting in immune response defects. Interestingly, recent findings report that DNMT3B shapes intragenic CpG-methylation of highly-transcribed genes. However, how the DNMT3B-dependent epigenetic network modulates transcription and whether ICF1-specific mutations impair this process remains unknown...
March 9, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28330812/molecular-evidence-for-differential-long-term-outcomes-of-early-life-severe-acute-malnutrition
#2
Allan Sheppard, Sherry Ngo, Xiaoling Li, Michael Boyne, Debbie Thompson, Anthony Pleasants, Peter Gluckman, Terrence Forrester
BACKGROUND: Severe acute malnutrition (SAM) in infants may present as one of two distinct syndromic forms: non-edematous (marasmus), with severe wasting and no nutritional edema; or edematous (kwashiorkor) with moderately severe wasting. These differences may be related to developmental changes prior to the exposure to SAM and phenotypic changes appear to persist into adulthood with differences between the two groups. We examined whether the different response to SAM and subsequent trajectories may be explained by developmentally-induced epigenetic differences...
March 8, 2017: EBioMedicine
https://www.readbyqxmd.com/read/28330758/regulation-of-type-i-interferon-signaling-in-immunity-and-inflammation-a-comprehensive-review
#3
REVIEW
Kun Chen, Juan Liu, Xuetao Cao
Type I interferons (IFNs) play essential roles in establishing and modulating host defense against microbial infection via induction of IFN-stimulated genes (ISGs) through Janus kinase (JAK)-signal transducer and activator of transcription (STAT) signaling pathway. However, dysregulation of IFNs production and function could also mediate immune pathogenesis such as inflammatory autoimmune diseases and infectious diseases via aberrantly activating inflammatory responses or improperly suppressing microbial controls...
March 19, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28324831/primary-and-acquired-resistance-to-pd-1-pd-l1-blockade-in-cancer-treatment
#4
REVIEW
Qiaohong Wang, Xia Wu
PD-1/PD-L1 blockade appears to be a very promising immunotherapy with significant clinical benefits and durable responses in multiple tumor types. However, the effectual clinical benefits of PD-1/PD-L1 blockade are hampered by a high rate of primary resistance, where patients do not respond to PD-1/PD-L1 blockade initially. And more distressingly, most patients eventually develop acquired resistance after an initial response to PD-1/PD-L1 blockade. The mechanisms underlying primary and acquired resistance to PD-1/PD-L1 blockade have remained ambiguous...
March 18, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28322583/interplay-between-genetic-and-epigenetic-mechanisms-in-rheumatoid-arthritis
#5
Mojca Frank-Bertoncelj, Kerstin Klein, Steffen Gay
Genetic and environmental factors contribute to the risk for rheumatoid arthritis (RA), with epigenetics serving as a possible interface through which risk factors contribute to RA. High-throughput technologies for interrogating genome and epigenome, and the availability of genetic and epigenetic datasets across a diversity of cell types, enable the identification of candidate causal genetic variants for RA to study their function in core RA processes. To date, RA risk variants were studied in the immune cells but not joint resident cells, for example, synovial fibroblasts...
March 21, 2017: Epigenomics
https://www.readbyqxmd.com/read/28320913/relationship-between-cd4-regulatory-t-cells-and-anergy-in-vivo
#6
REVIEW
Lokesh A Kalekar, Daniel L Mueller
Selective suppression of effector CD4(+) T cell functions is necessary to prevent immune cell-mediated damage to healthy tissues. This appears especially true during pregnancy or in individuals predisposed to autoimmunity. Foxp3(+) regulatory T (Treg) cells and induction of anergy, an acquired state of T cell functional unresponsiveness in Foxp3(-) cells, have both been implicated as mechanisms to suppress dangerous immune responses to tissue-restricted self-Ags. Anergic CD4(+) T cells and Treg cells share a number of phenotypic and mechanistic traits-including the expression of CD73 and folate receptor 4, and the epigenetic modification of Treg cell signature genes-and an interesting relationship between these two subsets has recently emerged...
April 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28315775/assessment-of-histone-tail-modifications-and-transcriptional-profiling-during-colon-cancer-progression-reveals-a-global-decrease-in-h3k4me3-activity
#7
Karen Triff, Mathew W McLean, Kranti Konganti, Jiahui Pang, Evelyn Callaway, Beiyan Zhou, Ivan Ivanov, Robert S Chapkin
During colon cancer, epigenetic alterations contribute to the dysregulation of major cellular functions and signaling pathways. Modifications in chromatin signatures such as H3K4me3 and H3K9ac, which are associated with transcriptionally active genes, can lead to genomic instability and perturb the expression of gene sets associated with oncogenic processes. In order to further elucidate early pre-tumorigenic epigenetic molecular events driving CRC, we integrated diverse, genome-wide, epigenetic inputs (by high throughput sequencing of RNA, H3K4me3, and H3K9ac) and compared differentially expressed transcripts (DE) and enriched regions (DER) in an in-vivo rat colon cancer progression model...
March 15, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28314406/the-role-of-targeted-therapy-in-the-management-of-sinonasal-malignancies
#8
REVIEW
Lawrence Kashat, Christopher H Le, Alexander G Chiu
Cancers develop secondary to genetic and epigenetic changes that provide the cell with a survival advantage that promotes cellular immortality. Malignancy arises when tumors use mechanisms to evade detection and destruction by the immune system. Many malignancies seem to elicit an immune response, yet somehow manage to avoid destruction by the cells of the immune system. Cancers may evade this immune response by numerous mechanisms. Several targeted immune therapies are available that block some of these inhibitory signals and enhance the cell-mediated immune response...
April 2017: Otolaryngologic Clinics of North America
https://www.readbyqxmd.com/read/28303495/genetic-landscape-and-classification-of-peripheral-t-cell-lymphomas
#9
REVIEW
Rosalind F Sandell, Rebecca L Boddicker, Andrew L Feldman
PURPOSE OF REVIEW: Peripheral T cell lymphomas (PTCLs) are markedly heterogeneous at the clinical, pathological, and molecular levels. This review will discuss genetic findings in PTCL with special emphasis on how they impact lymphoma classification. RECENT FINDINGS: Sequencing studies have identified recurrent genetic alterations in nearly every PTCL subtype. In anaplastic large cell lymphoma, these studies have revealed novel chromosomal rearrangements and mutations that have prognostic significance and may suggest new therapeutic approaches...
April 2017: Current Oncology Reports
https://www.readbyqxmd.com/read/28298276/early-life-nutritional-programming-of-cognition-the-fundamental-role-of-epigenetic-mechanisms-in-mediating-the-relation-between-early-life-environment-and-learning-and-memory-process
#10
REVIEW
Laura Moody, Hong Chen, Yuan-Xiang Pan
The perinatal period is a window of heightened plasticity that lays the groundwork for future anatomic, physiologic, and behavioral outcomes. During this time, maternal diet plays a pivotal role in the maturation of vital organs and the establishment of neuronal connections. However, when perinatal nutrition is either lacking in specific micro- and macronutrients or overloaded with excess calories, the consequences can be devastating and long lasting. The brain is particularly sensitive to perinatal insults, with several neurologic and psychiatric disorders having been linked to a poor in utero environment...
March 2017: Advances in Nutrition
https://www.readbyqxmd.com/read/28293926/prenatal-maternal-distress-and-allergic-diseases-in-offspring-review-of-evidence-and-possible-pathways
#11
REVIEW
Dong In Suh, Hyoung Yoon Chang, Eun Lee, Song I Yang, Soo Jong Hong
Recent studies have suggested a close association between prenatal maternal distress and allergic diseases in the offspring. We selected relevant birth-cohort or national registry studies using a keyword search of the PubMed database and summarized current evidence on the impact of prenatal maternal distress on the development of offspring's allergic diseases. Moreover, we postulated possible pathways linking prenatal distress and allergic diseases based on relevant human and animal studies. Both dysregulated hypothalamic-pituitary-adrenal axis and increased oxidative stress may cause structural (altered brain/lung development) and functional (skewed immune development) changes, which may predispose the fetus to developing allergic diseases during childhood...
May 2017: Allergy, Asthma & Immunology Research
https://www.readbyqxmd.com/read/28290496/transcriptome-analysis-of-a-wild-bird-reveals-physiological-responses-to-the-urban-environment
#12
Hannah Watson, Elin Videvall, Martin N Andersson, Caroline Isaksson
Identifying the molecular basis of environmentally induced phenotypic variation presents exciting opportunities for furthering our understanding of how ecological processes and the environment can shape the phenotype. Urban and rural environments present free-living organisms with different challenges and opportunities, which have marked consequences for the phenotype, yet little is known about responses at the molecular level. We characterised transcriptomes from an urban and a rural population of great tits Parus major, demonstrating striking differences in gene expression profiles in both blood and liver tissues...
March 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28284523/demethylase-kdm6a-epigenetically-promotes-il-6-and-ifn-%C3%AE-production-in-macrophages
#13
Xia Li, Qian Zhang, Qingzhu Shi, Yin Liu, Kai Zhao, Qicong Shen, Yang Shi, Xingguang Liu, Chunmei Wang, Nan Li, Yuanfang Ma, Xuetao Cao
Molecular regulation of innate signal-initiated proinflammatory cytokine production has been extensively investigated. However, the roles of epigenetic modifiers and their underlying mechanisms in regulating innate inflammatory response and development of autoimmune diseases need to be further understood. Demethylase Kdm6a promotes gene transcription in cell-lineage specification through demethylating histone H3 lysine di/tri-methylation (H3K27me2/3), and loss of Kdm6a results in developmental defects. However, the function of Kdm6a in innate immunity and inflammation remains largely unknown...
March 8, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28280003/epigenetic-memory-in-response-to-environmental-stressors
#14
Paolo Vineis, Aristotelis Chatziioannou, Vincent T Cunliffe, James M Flanagan, Mark Hanson, Micheline Kirsch-Volders, Soterios Kyrtopoulos
Exposure to environmental stressors, toxicants, and nutrient deficiencies can affect DNA in several ways. Some exposures cause damage and alter the structure of DNA, but there is increasing evidence that the same or other environmental exposures, including those that occur during fetal development in utero, can cause epigenetic effects that modulate DNA function and gene expression. Some epigenetic changes to DNA that affect gene transcription are at least partially reversible (i.e., they can be enzymatically reversed after cessation of exposure to environmental agents), but some epigenetic modifications seem to persist, even for decades...
March 9, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28276156/retinoic-acid-inducible-gene-1-protein-rig1-like-receptor-pathway-is-required-for-efficient-nuclear-reprogramming
#15
Nazish Sayed, Frank Ospino, Farhan Himmati, Jieun Lee, Palas Chanda, Edward S Mocarski, John P Cooke
We have revealed a critical role for innate immune signaling in nuclear reprogramming to pluripotency, and in the nuclear reprogramming required for somatic cell transdifferentiation. Activation of innate immune signaling causes global changes in the expression and activity of epigenetic modifiers to promote epigenetic plasticity. In our previous papers, we focused on the role of toll-like receptor 3 (TLR3) in this signaling pathway. Here we define the role of another innate immunity pathway known to participate in the response to viral RNA, the retinoic acid-inducible gene 1 receptor (RIG-1)-like receptor (RLR) pathway...
March 9, 2017: Stem Cells
https://www.readbyqxmd.com/read/28273193/-drug-therapy-of-lymphomas
#16
Lajos Gergely
The therapy of lymphomas has undergone a major expansion during the last decade. Novel therapeutic targets have appeared beyond classical chemotherapeutic combinations. These novel drugs have very pronounced action across lymphoma types, and their toxicity profile is usually better tolerable compared to standard chemotherapies. These new therapies are enabling us to offer treatment to those patients who have refractory disease, and we had no option to treat them before these drugs. The author describes several new therapeutic options...
March 8, 2017: Magyar Onkologia
https://www.readbyqxmd.com/read/28271497/chronic-schistosomiasis-during-pregnancy-epigenetically-reprograms-t-cell-differentiation-in-offspring-of-infected-mothers
#17
Kathrin Klar, Sophie Perchermeier, Sonakshi Bhattacharjee, Hani Harb, Thure Adler, Rouzanna Istvanffy, Eva Loffredo-Verde, Robert Oostendorp, Harald Renz, Clarissa Prazeres da Costa
Schistosomiasis is a non-transplacental helminth infection. Chronic infection during pregnancy suppresses allergic airway responses in offspring. We addressed the question whether in utero exposure to chronic schistosome infection (Reg phase) in mice affects B cell and T cell development. Therefore, we focused our analysis on T cell differentiation capacity induced by epigenetic changes in promoter regions of signature cytokines in offspring. Here we show that naïve T cells from offspring of schistosome infected female mice had a strong capacity to differentiate into TH 1 cells, whereas TH 2 differentiation was impaired...
March 8, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28228641/evaluation-of-trained-immunity-by-%C3%AE-1-3-d-glucan-on-murine-monocytes-in-vitro-and-duration-of-response-in-vivo
#18
Pablo Garcia-Valtanen, Ruth Marian Guzman-Genuino, David L Williams, John D Hayball, Kerrilyn R Diener
The β-1, 3 (d)-glucan (β-glucan) present in the cell wall of Candida albicans induces epigenetic changes in human monocytes resulting in primed macrophages exhibiting increased cytokine responsiveness to reinfection. This phenomenon is referred to as trained immunity or innate immune memory. However, whether β-glucan can reprogramme murine monocytes in vitro or induce lasting effects in vivo has yet to be elucidated. Thus, purified murine spleen-derived monocytes were primed with β-glucan in vitro and assessed for markers of differentiation and survival...
March 14, 2017: Immunology and Cell Biology
https://www.readbyqxmd.com/read/28220199/-novel-pharmaceutical-treatment-approaches-for-gastric-cancer
#19
F Lordick
This review article delineates novel approaches for the pharmaceutical treatment of gastric cancer. A newly developed molecular classification of gastric cancer based on histology, genetic, epigenetic and proteomic characteristics has evolved. It provides a road map for development of new drugs and combinations as well as for patient stratification in clinical research and it is expected to be introduced into clinical practice in the near future. Anti-HER2 targeted treatment is a validated strategy for treatment of metastatic gastric cancer and is now also being studied in the perioperative setting to increase response rates and ultimately survival in patients undergoing curative surgery; however, the resistance mechanisms of HER2-targeted treatment are poorly understood and optimal patient selection remains challenging...
February 20, 2017: Der Pathologe
https://www.readbyqxmd.com/read/28219335/stress-responsive-pathways-and-small-rna-changes-distinguish-variable-developmental-phenotypes-caused-by-msh1-loss
#20
Mon-Ray Shao, Sunil Kumar Kenchanmane Raju, John D Laurie, Robersy Sanchez, Sally A Mackenzie
BACKGROUND: Proper regulation of nuclear-encoded, organelle-targeted genes is crucial for plastid and mitochondrial function. Among these genes, MutS Homolog 1 (MSH1) is notable for generating an assortment of mutant phenotypes with varying degrees of penetrance and pleiotropy. Stronger phenotypes have been connected to stress tolerance and epigenetic changes, and in Arabidopsis T-DNA mutants, two generations of homozygosity with the msh1 insertion are required before severe phenotypes begin to emerge...
February 20, 2017: BMC Plant Biology
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