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Epigenetics immune response

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https://www.readbyqxmd.com/read/28088983/the-epigenetic-basis-of-hematopoietic-stem-cell-aging
#1
REVIEW
Ashley Kramer, Grant A Challen
Highly proliferative tissues such as the gut, skin, and bone marrow lose millions of cells each day to normal attrition and challenge from different biological adversities. To achieve a lifespan beyond the longevity of individual cell types, tissue-specific stem cells sustain these tissues throughout the life of a human. For example, the lifespan of erythrocytes is about 100 days and adults make about two million new erythrocytes every second. A small pool of hematopoietic stem cells (HSCs) in the bone marrow is responsible for the lifetime maintenance of these populations...
January 2017: Seminars in Hematology
https://www.readbyqxmd.com/read/28074830/tet1-in-nucleus-accumbens-opposes-depression-and-anxiety-like-behaviors
#2
Jian Feng, Catherine J Pena, Immanuel Purushothaman, Olivia Engmann, Deena Walker, Amber N Brown, Orna Issler, Marie Doyle, Eileen Harrigan, Ezekiell Mouzon, Vincent Vialou, Li Shen, Meelad M Dawlaty, Rudolf Jaenisch, Eric J Nestler
Depression is a leading cause of disease burden, yet current therapies fully treat <50% of affected individuals. Increasing evidence implicates epigenetic mechanisms in depression and antidepressant action. Here, we examined a possible role for the DNA dioxygenase, ten eleven translocation protein 1 (TET1), in depression-related behavioral abnormalities. We applied chronic social defeat stress, an ethologically validated mouse model of depression-like behaviors, and examined Tet1 expression changes in nucleus accumbens (NAc), a key brain reward region...
January 11, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28074529/epigenetic-mediated-immune-suppression-of-positive-co-stimulatory-molecules-in-chemoresistant-ovarian-cancer-cells
#3
Ercan Cacan
The immunological response against cancer is a critical balance between immune-activating and immune-suppressing mechanisms. Ovarian cancer creates a suppressive microenvironment to escape immune elimination; however, the molecular mechanisms are poorly understood, and it is unclear whether chemotherapeutic drugs exert an immunoreactive or immunosuppressive effect on the tumor microenvironment. 4-1BB ligand (4-1BBL/CD157) and OX-40 ligand (OX-40L/CD252) are important regulators of effector cytotoxic T-cells activity...
January 11, 2017: Cell Biology International
https://www.readbyqxmd.com/read/28070760/the-generation-r-study-design-and-cohort-update-2017
#4
Marjolein N Kooijman, Claudia J Kruithof, Cornelia M van Duijn, Liesbeth Duijts, Oscar H Franco, Marinus H van IJzendoorn, Johan C de Jongste, Caroline C W Klaver, Aad van der Lugt, Johan P Mackenbach, Henriëtte A Moll, Robin P Peeters, Hein Raat, Edmond H H M Rings, Fernando Rivadeneira, Marc P van der Schroeff, Eric A P Steegers, Henning Tiemeier, André G Uitterlinden, Frank C Verhulst, Eppo Wolvius, Janine F Felix, Vincent W V Jaddoe
The Generation R Study is a population-based prospective cohort study from fetal life until adulthood. The study is designed to identify early environmental and genetic causes and causal pathways leading to normal and abnormal growth, development and health from fetal life, childhood and young adulthood. This multidisciplinary study focuses on several health outcomes including behaviour and cognition, body composition, eye development, growth, hearing, heart and vascular development, infectious disease and immunity, oral health and facial growth, respiratory health, allergy and skin disorders of children and their parents...
December 2016: European Journal of Epidemiology
https://www.readbyqxmd.com/read/28062906/programmed-cell-death-1-pathway-inhibition-in-myeloid-malignancies-implications-for-myeloproliferative-neoplasms
#5
REVIEW
D C Choi, D Tremblay, C Iancu-Rubin, J Mascarenhas
Myeloproliferative neoplasms (MPNs) are clonal hematopoietic diseases that belong to the spectrum of myeloid malignancies (MyMs), which also include myelodysplastic syndromes (MDS), acute myeloid leukemia (AML), and chronic myelogenous leukemia (CML). While hematopoietic stem cell transplantation (HSCT) is a potentially curative therapeutic approach to many MyMs, the associated morbidity and mortality have necessitated the development of non-HSCT therapeutics for symptom management and disease course modification...
January 6, 2017: Annals of Hematology
https://www.readbyqxmd.com/read/28057216/histone-acetylation-and-the-regulation-of-major-histocompatibility-class-ii-gene-expression
#6
K Suzuki, Y Luo
Major histocompatibility complex (MHC) class II molecules are essential for processing and presenting exogenous pathogen antigens to activate CD4(+) T cells. Given their central role in adaptive immune responses, MHC class II genes are tightly regulated in a tissue- and activation-specific manner. The regulation of MHC class II gene expression involves various transcription factors that interact with conserved proximal cis-acting regulatory promoter elements, as well as MHC class II transactivator that interacts with a variety of chromatin remodeling machineries...
2017: Advances in Protein Chemistry and Structural Biology
https://www.readbyqxmd.com/read/28057215/the-role-of-epigenetic-regulation-in-transcriptional-memory-in-the-immune-system
#7
A M Woodworth, A F Holloway
The immune system is exquisitely poised to identify, respond to, and eradicate pathogens from the body, as well as to produce a more rapid and augmented response to a subsequent encounter with the pathogen. These cellular responses rely on the highly coordinated and rapid activation of gene expression programs as well as the ability of the cell to retain a memory of the initial gene response. It is clear that chromatin structure and epigenetic mechanisms play a crucial role in determining these gene responses, and in fact the immune system has proved an instructive model for investigating the multifaceted mechanisms through which the chromatin landscape contributes to gene expression programs...
2017: Advances in Protein Chemistry and Structural Biology
https://www.readbyqxmd.com/read/28057213/a-new-molecular-mechanism-underlying-the-antitumor-effect-of-dna-methylation-inhibitors-via-an-antiviral-immune-response
#8
Y Saito, T Nakaoka, H Saito
Chromatin remodeling mediated by DNA methylation and histone modifications play critical roles in the transcriptional regulation of protein-coding genes, noncoding RNAs such as microRNAs, and endogenous retroviruses (ERVs). Many studies have shown that aberrant DNA methylation and histone modifications are associated with the initiation and progression of various malignancies. Epigenetic silencing of tumor suppressor genes in cancer is generally mediated by DNA hypermethylation of CpG island promoters and histone modifications such as histone deacetylation, methylation of histone H3 lysine 9 (H3K9), and trimethylation of H3K27...
2017: Advances in Protein Chemistry and Structural Biology
https://www.readbyqxmd.com/read/28057212/regulation-of-cellular-immune-responses-in-sepsis-by-histone-modifications
#9
W F Carson, S L Kunkel
Severe sepsis, septic shock, and related inflammatory syndromes are driven by the aberrant expression of proinflammatory mediators by immune cells. During the acute phase of sepsis, overexpression of chemokines and cytokines drives physiological stress leading to organ failure and mortality. Following recovery from sepsis, the immune system exhibits profound immunosuppression, evidenced by an inability to produce the same proinflammatory mediators that are required for normal responses to infectious microorganisms...
2017: Advances in Protein Chemistry and Structural Biology
https://www.readbyqxmd.com/read/28045112/bromodomain-protein-brd3-promotes-ifnb1-transcription-via-enhancing-irf3-p300-complex-formation-and-recruitment-to-ifnb1-promoter-in-macrophages
#10
Wenhui Ren, Chunmei Wang, Qinlan Wang, Dezhi Zhao, Kai Zhao, Donghao Sun, Xingguang Liu, Chaofeng Han, Jin Hou, Xia Li, Qian Zhang, Xuetao Cao, Nan Li
As members of bromodomain and extra-terminal motif protein family, bromodomain-containing proteins regulate a wide range of biological processes including protein scaffolding, mitosis, cell cycle progression and transcriptional regulation. The function of these bromodomain proteins (Brds) in innate immune response has been reported but the role of Brd3 remains unclear. Here we find that virus infection significantly downregulate Brd3 expression in macrophages and Brd3 knockout inhibits virus-triggered IFN-β production...
January 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28034764/the-concept-of-the-personal-vitamin-d-response-index
#11
REVIEW
Carsten Carlberg, Afrozul Haq
Humans are able to synthesize vitamin D3 in their skin when exposed to UV-B, but seasonal variations, textile coverage and predominant indoor activities often make supplementation with the compound necessary. There is some dispute on the desired vitamin D status, measured via the serum concentration of the most stable vitamin D3 metabolite, 25-hydroxyvitamin D3, and the respective recommended daily supplementation. A possible answer may be provided by the concept of the personal vitamin D response index describing the efficiency of the molecular response to supplementation with vitamin D...
December 26, 2016: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28031014/cebp-epigenetic-dysregulation-as-a-drug-target-for-the-treatment-of-hematologic-and-gynecologic-malignancies
#12
Chengming Sun, Ping Duan, Caifu Luan
The CCAAT/enhancer binding proteins (C/EBPs) form a family of transcription factors regulating many genes' expression in a variety of cells/tissues/organs at different developmental stages. With their capability of binding to a loosely defined consensus DNA sequence and through extensive protein-protein interactions, C/EBPs modulate diverse functions including cell differentiation, metabolism, and immune response, under both physiological and pathological conditions such as the establishment of hematological lineages, the maintenance of normal reproductive function, and the development of malignant disease...
December 28, 2016: Current Drug Targets
https://www.readbyqxmd.com/read/28026094/phenotypic-characteristics-of-aged-cd4-cd28-null-t-lymphocytes-are-determined-by-changes-in-the-whole-genome-dna-methylation-pattern
#13
Beatriz Suarez-Álvarez, Ramón M Rodríguez, Karin Schlangen, Aroa Baragaño Raneros, Leonardo Márquez-Kisinousky, Agustín F Fernández, Carmen Díaz-Corte, Ana M Aransay, Carlos López-Larrea
Aging is associated with a progressive loss of the CD28 costimulatory molecule in CD4(+) lymphocytes (CD28(null) T cells), which is accompanied by the acquisition of new biological and functional properties that give rise to an impaired immune response. The regulatory mechanisms that govern the appearance and function of this cell subset during aging and in several associated inflammatory disorders remain controversial. Here, we present the whole-genome DNA methylation and gene expression profiles of CD28(null) T cells and its CD28(+) counterpart...
December 27, 2016: Aging Cell
https://www.readbyqxmd.com/read/28018352/the-capricious-nature-of-bacterial-pathogens-phasevarions-and-vaccine-development
#14
REVIEW
Aimee Tan, John M Atack, Michael P Jennings, Kate L Seib
Infectious diseases are a leading cause of morbidity and mortality worldwide, and vaccines are one of the most successful and cost-effective tools for disease prevention. One of the key considerations for rational vaccine development is the selection of appropriate antigens. Antigens must induce a protective immune response, and this response should be directed to stably expressed antigens so the target microbe can always be recognized by the immune system. Antigens with variable expression, due to environmental signals or phase variation (i...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/28018344/adjunct-strategies-for-tuberculosis-vaccines-modulating-key-immune-cell-regulatory-mechanisms-to-potentiate-vaccination
#15
REVIEW
Lakshmi Jayashankar, Richard Hafner
Tuberculosis (TB) remains a global health threat of alarming proportions, resulting in 1.5 million deaths worldwide. The only available licensed vaccine, Bacillus Calmette-Guérin, does not confer lifelong protection against active TB. To date, development of an effective vaccine against TB has proven to be elusive, and devising newer approaches for improved vaccination outcomes is an essential goal. Insights gained over the last several years have revealed multiple mechanisms of immune manipulation by Mycobacterium tuberculosis (Mtb) in infected macrophages and dendritic cells that support disease progression and block development of protective immunity...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/28009152/lung-tumors-copd-and-immune-response-is-epigenetics-the-bottom-line
#16
Elisabetta Balestro, Simonetta Baraldo, Davide Piloni, Giulia M Stella
NSCLC is a heterogeneous disorder consisting of distinct molecular subtypes which can be treated by using specific drugs targeted to distinct genetic lesions. It is well known that NSCLS incidence is higher in chronic obstructive pulmonary disease (COPD) patients because they share a common risk factor (cigarette smoking) and it is believed that the typical inflammatory microenvironment observed in COPD may influence the molecular mechanisms responsible of carcinogenesis. In the last years, the role of epigenetic processes in cell biology and tissue pathology has been extensively studied both in COPD and NSCLC...
December 2016: Minerva Medica
https://www.readbyqxmd.com/read/28000527/epigenetic-regulation-of-immune-checkpoints-another-target-for-cancer-immunotherapy
#17
Mahmoud A Ali, Marwa Matboli, Marwa Tarek, Maged Reda, Kamal M Kamal, Mahmoud Nouh, Ahmed M Ashry, Ahmed Fath El-Bab, Hend A Mesalam, Ayman El-Sayed Shafei, Omar Abdel-Rahman
Epigenetic changes in oncogenes and tumor-suppressor genes contribute to carcinogenesis. Understanding the epigenetic and genetic components of tumor immune evasion is crucial. Few cancer genetic mutations have been linked to direct correlations with immune evasion. Studies on the epigenetic modulation of the immune checkpoints have revealed a critical interaction between epigenetic and immune modulation. Epigenetic modifiers can activate many silenced genes. Some of them are immune checkpoints regulators that turn on immune responses and others turn them off resulting in immune evasion...
January 2017: Immunotherapy
https://www.readbyqxmd.com/read/27999745/microrna-155-deficiency-impairs-dendritic-cell-function-in-breast-cancer
#18
Junfeng Wang, Stephen Iwanowycz, Fang Yu, Xuemei Jia, Shuilong Leng, Yuzhen Wang, Wei Li, Shiang Huang, Walden Ai, Daping Fan
In antitumor immunity, dendritic cells (DCs) capture, process, and present tumor antigens to T cells, initiating a tumoricidal response. However, DCs are often dysfunctional due to their exposure to the tumor microenvironment (TME), leading to tumor escape from immune surveillance. Here, a vital role of microRNA-155 (miR-155) in regulating the function of DCs in breast cancer is reported. Host miR-155 deficiency enhanced breast cancer growth in mice, accompanied by reduced DCs in the tumors and draining lymph nodes...
2016: Oncoimmunology
https://www.readbyqxmd.com/read/27997080/prevention-of-allograft-rejection-by-use-of-regulatory-t-cells-with-a-mhc-specific-chimeric-antigen-receptor
#19
F Noyan, K Zimmermann, M Hardtke-Wolenski, A Knoefel, E Schulde, R Geffers, M Hust, J Huehn, M Galla, M Morgan, A Jokuszies, M P Manns, E Jaeckel
CD4+CD25highFOXP3+ regulatory T cells (Tregs) are involved in graft-specific tolerance after solid organ transplantation. However, adoptive transfer of polyspecific Tregs alone is insufficient to prevent graft rejection even in rodent models, indicating that graft-specific Tregs are required. We developed a highly specific chimeric antigen receptor that recognizes the HLA molecule A*02 (referred to as A2-CAR). Transduction into nTregs changes the specificity of the nTregs without alteration of their regulatory phenotype and epigenetic stability...
December 20, 2016: American Journal of Transplantation
https://www.readbyqxmd.com/read/27989961/role-of-mineralocorticoid-receptor-activation-in-cardiac-diastolic-dysfunction
#20
REVIEW
Guanghong Jia, Yan Jia, James R Sowers
The prevalence of cardiac diastolic dysfunction and heart failure with preserved ejection, a major cause of morbidity and mortality in the western world, is increasing due, in part, to increases in obesity and type 2 diabetes. Characteristics of cardiac diastolic dysfunction include increased myocardial stiffness and impaired left ventricular (LV) relaxation that is characterized by prolonged isovolumic LV relaxation and slow LV filling. Obesity, insulin resistance and type 2 diabetes, especially in females promote activation of mineralocorticoid receptor (MR) signaling with resultant increases in oxidative stress, maladaptive immune responses, inflammation, and impairment of coronary blood flow and cardiac interstitial fibrosis...
October 28, 2016: Biochimica et Biophysica Acta
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