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https://www.readbyqxmd.com/read/27914308/regulation-of-t-helper-cell-differentiation-by-e3-ubiquitin-ligases-and-deubiquitinating-enzymes
#1
REVIEW
Si-Fa Gao, Bo Zhong, Dandan Lin
CD4 T cells are essential components of adaptive immunity and play a critical role in anti-pathogenic or anti-tumor responses as well as autoimmune and allergic diseases. Naive CD4 T cells differentiate into distinct subsets of T helper (Th) cells by various signals including TCR, costimulatory and cytokine signals. Accumulating evidence suggests that these signaling pathways are critically regulated by ubiquitination and deubiquitination, two reversible posttranslational modifications mediated by E3 ubiquitin ligases and deubiquitinating enzymes (DUBs), respectively...
November 30, 2016: International Immunopharmacology
https://www.readbyqxmd.com/read/27913516/immunoregulatory-networks-in-sickle-cell-alloimmunization
#2
Karina Yazdanbakhsh
Red blood cell (RBC) transfusions are critical for treatment and prevention of complications of sickle cell disease (SCD), and most SCD patients will receive 1 or more transfusions by age 20. However, SCD alloimmunization remains a serious complication of transfusions that can lead to life-threatening acute and delayed transfusion reactions. Alloimmunization rates are higher in SCD patients most likely due to RBC antigenic differences between largely white donors vs mainly African-American recipients and frequency of transfusions...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27912316/th2-cells-in-health-and-disease
#3
Toshinori Nakayama, Kiyoshi Hirahara, Atsushi Onodera, Yusuke Endo, Hiroyuki Hosokawa, Kenta Shinoda, Damon J Tumes, Yoshitaka Okamoto
Helper T (Th) cell subsets direct immune responses by producing signature cytokines. Th2 cells produce IL-4, IL-5, and IL-13, which are important in humoral immunity and protection from helminth infection and are central to the pathogenesis of many allergic inflammatory diseases. Molecular analysis of Th2 cell differentiation and maintenance of function has led to recent discoveries that have refined our understanding of Th2 cell biology. Epigenetic regulation of Gata3 expression by chromatin remodeling complexes such as Polycomb and Trithorax is crucial for maintaining Th2 cell identity...
November 28, 2016: Annual Review of Immunology
https://www.readbyqxmd.com/read/27912146/inosine-acedoben-dimepranol-promotes-an-early-and-sustained-increase-in-the-natural-killer-cell-component-of-circulating-lymphocytes-a-clinical-trial-supporting-anti-viral-indications
#4
S Rumel Ahmed, Amy S Newman, James O'Daly, Sean Duffy, Gillian Grafton, Catherine A Brady, S John Curnow, Nicholas M Barnes, John Gordon
Inosine Acedoben Dimepranol (IAD), licensed for the treatment of cell-mediated immune deficiencies associated with viral infections, has been reported to impact a variety of immune parameters both in vitro and in vivo. Here we report the results from a clinical trial where multiple lymphocyte subsets - CD19+ B cells, CD3+ T cells, CD4+ T-helper cells, FoxP3(hi)/CD25(hi)/CD127(lo) regulatory T cells (Tregs), CD3-/CD56+ NK cells, and CD3+/CD56+ NKT cells - were, together with serum immunoglobulins and IgG subclasses, followed during 14days of IAD administration to ten healthy volunteers; these selected from 27 individuals pre-screened in vitro for their capacity to respond to IAD as gauged by increases in the percentage of Treg and/or NKT cells arising in PHA-stimulated cultures...
November 29, 2016: International Immunopharmacology
https://www.readbyqxmd.com/read/27911796/egr2-and-egr3-in-regulatory-t-cells-cooperatively-control-systemic-autoimmunity-through-ltbp3-mediated-tgf-%C3%AE-3-production
#5
Kaoru Morita, Tomohisa Okamura, Mariko Inoue, Toshihiko Komai, Shuzo Teruya, Yukiko Iwasaki, Shuji Sumitomo, Hirofumi Shoda, Kazuhiko Yamamoto, Keishi Fujio
Systemic lupus erythematosus (SLE) is a prototypical autoimmune disease characterized by multiorgan inflammation induced by autoantibodies. Early growth response gene 2 (Egr2), a transcription factor essential for T-cell anergy induction, controls systemic autoimmunity in mice and humans. We have previously identified a subpopulation of CD4(+) regulatory T cells, CD4(+)CD25(-)LAG3(+) cells, that characteristically express both Egr2 and LAG3 and control mice model of lupus via TGF-β3 production. However, due to the mild phenotype of lymphocyte-specific Egr2-deficient mice, the presence of an additional regulator has been speculated...
November 30, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27909575/a-step-by-step-workflow-for-low-level-analysis-of-single-cell-rna-seq-data
#6
Aaron T L Lun, Davis J McCarthy, John C Marioni
Single-cell RNA sequencing (scRNA-seq) is widely used to profile the transcriptome of individual cells. This provides biological resolution that cannot be matched by bulk RNA sequencing, at the cost of increased technical noise and data complexity. The differences between scRNA-seq and bulk RNA-seq data mean that the analysis of the former cannot be performed by recycling bioinformatics pipelines for the latter. Rather, dedicated single-cell methods are required at various steps to exploit the cellular resolution while accounting for technical noise...
2016: F1000Research
https://www.readbyqxmd.com/read/27908305/abatacept-treatment-of-patients-with-primary-sj%C3%A3-gren-s-syndrome-results-in-a-decrease-of-germinal-centres-in-salivary-gland-tissue
#7
Erlin A Haacke, Bert van der Vegt, Petra M Meiners, Arjan Vissink, Fred K L Spijkervet, Hendrika Bootsma, Frans G M Kroese
OBJECTIVES: The aim of this study was to assess the histopathological changes in parotid gland tissue of primary Sjögren's syndrome (pSS) patients treated with abatacept. METHODS: In all 15 pSS patients included in the open-label Active Sjögren Abatacept Pilot (ASAP, 8 abatacept infusions) study parotid gland biopsies were taken before treatment and at 24 weeks of follow up. Biopsies were analysed for pSS-related histopathological features and placed in context of clini- cal responsiveness as assessed with EULAR Sjögren's syndrome disease activity index (ESSDAI)...
November 12, 2016: Clinical and Experimental Rheumatology
https://www.readbyqxmd.com/read/27905107/co-operative-suppression-of-inflammatory-responses-in-human-dendritic-cells-by-plant-proanthocyanidins-and-products-from-the-parasitic-nematode-trichuris-suis
#8
Andrew R Williams, Elsenoor J Klaver, Lisa C Laan, Aina Ramsay, Christos Fryganas, Rolf Difborg, Helene Kringel, Jess D Reed, Irene Mueller-Harvey, Søren Skov, Irma van Die, Stig M Thamsborg
Interactions between dendritic cells (DCs) and environmental, dietary and pathogen antigens play a key role in immune homeostasis and regulation of inflammation. Dietary polyphenols such as proanthocyanidins (PAC) may reduce inflammation, and we therefore hypothesized that PAC may suppress lipopolysaccharide (LPS) -induced responses in human DCs and subsequent T helper type 1 (Th1) -type responses in naive T cells. Moreover, we proposed that, because DCs are likely to be exposed to multiple stimuli, the activity of PAC may synergise with other bioactive molecules that have anti-inflammatory activity, e...
November 7, 2016: Immunology
https://www.readbyqxmd.com/read/27903079/preclinical-evaluation-of-a-replication-deficient-recombinant-adenovirus-serotype-5-vaccine-expressing-guanylate-cyclase-c-and-the-padre-t-helper-epitope
#9
Adam Eugene Snook, Trevor R Baybutt, Terry Hyslop, Scott Arthur Waldman
There is an unmet need for improved therapeutics for colorectal cancer, the second leading cause of cancer mortality worldwide. Adjuvant chemotherapy only marginally improves survival in some patients, and has no benefit in others, underscoring the clinical opportunity for novel immunotherapeutic approaches to improve survival in colorectal cancer. In that context, guanylate cyclase C (GUCY2C) is an established biomarker and therapeutic target for metastatic colorectal cancer with immunological characteristics that promote durable antitumor efficacy without autoimmunity...
November 30, 2016: Human Gene Therapy Methods
https://www.readbyqxmd.com/read/27902998/autoimmune-cytopenias-diagnosis-management
#10
Christian P Nixon, Joseph D Sweeney
The autoimmune cytopenias are a related group of disorders in which differentiated hematopoietic cells are destroyed by the immune system. Single lineage disease is characterized by the production of autoantibodies against red cells (autoimmune hemolytic anemia [AIHA]), platelets (autoimmune thrombocytopenia [ITP]) and neutrophils (autoimmune neutropenia [AIN]) whereas multilineage disease may include various combinations of these conditions. Central to the genesis of this disease is the breakdown of central and/or peripheral tolerance, and the subsequent production of autoantibodies by both tissue and circulating self-reactive B lymphocytes with support from T helper lymphocytes...
December 1, 2016: Rhode Island Medical Journal
https://www.readbyqxmd.com/read/27902996/pemphigus-pathogenesis-to-treatment
#11
Christopher DiMarco
Pemphigus vulgaris (PV), pemphigus foliaceus (PF), and paraneoplastic pemphigus (PNP) are a group of rare and fatal blistering diseases involving autoantibodies that target desmosomal proteins. The pathogenesis of pemphigus involves the production of activated B-cells and IgG with stimulation by IL-4 by T-helper 2 cells. Clinically these diseases present most often with epidermal erosions of the mucosae and skin caused by rapid rupturing of flaccid bullae. These lesions correlate histologically with splits forming in the epidermis, leaving a blister roof composed of a few cell layers...
December 1, 2016: Rhode Island Medical Journal
https://www.readbyqxmd.com/read/27902985/disease-manifestation-and-inflammatory-activity-as-modulators-of-th17-treg-balance-and-rorc-foxp3-methylation-in-systemic-sclerosis
#12
Giovanni Almanzar, Matthias Klein, Marc Schmalzing, Deborah Hilligardt, Nady El Hajj, Hermann Kneitz, Vanessa Wild, Andreas Rosenwald, Sandrine Benoit, Henning Hamm, Hans-Peter Tony, Thomas Haaf, Matthias Goebeler, Martina Prelog
BACKGROUND: There is much evidence that T cells are strongly involved in the pathogenesis of localized and systemic forms of scleroderma (SSc). A dysbalance between FoxP3+ regulatory CD4+ T cells (Tregs) and inflammatory T-helper (Th) 17 cells has been suggested. METHODS: The study aimed (1) to investigate the phenotypical and functional characteristics of Th17 and Tregs in SSc patients depending on disease manifestation (limited vs. diffuse cutaneous SSc, dcSSc) and activity, and (2) the transcriptional level and methylation status of Th17- and Treg-specific transcription factors...
December 1, 2016: International Archives of Allergy and Immunology
https://www.readbyqxmd.com/read/27902485/impacts-of-cigarette-smoking-on-immune-responsiveness-up-and-down-or-upside-down
#13
REVIEW
Feifei Qiu, Chun-Ling Liang, Huazhen Liu, Yu-Qun Zeng, Shaozhen Hou, Song Huang, Xiaoping Lai, Zhenhua Dai
Cigarette smoking is associated with numerous diseases and poses a serious challenge to the current healthcare system worldwide. Smoking impacts both innate and adaptive immunity and plays dual roles in regulating immunity by either exacerbation of pathogenic immune responses or attenuation of defensive immunity. Adaptive immune cells affected by smoking mainly include T helper cells (Th1/Th2/Th17), CD4+CD25+ regulatory T cells, CD8+ T cells, B cells and memory T/B lymphocytes while innate immune cells impacted by smoking are mostly DCs, macrophages and NK cells...
November 25, 2016: Oncotarget
https://www.readbyqxmd.com/read/27902353/corrigendum-to-follicular-helper-t-cells-and-virus-specific-antibody-response-in-primary-and-reactivated-human-cytomegalovirus-infections-of-the-immunocompetent-and-immunocompromised-transplant-patients
#14
Francesca Bruno, Chiara Fornara, Paola Zelini, Milena Furione, Elena Carrara, Lucia Scaramuzzi, Ilaria Cane, Federico Mele, Federica Sallusto, Daniele Lilleri, Giuseppe Gerna
No abstract text is available yet for this article.
October 2016: Journal of General Virology
https://www.readbyqxmd.com/read/27902338/recombinant-rabies-virus-expressing-il-21-enhances-immunogenicity-through-activation-of-t-follicular-helper-cells-and-germinal-center-b-cells
#15
Yajing Zhang, Ming Zhou, Zhao Wang, Jie Yang, Mingming Li, Kunlun Wang, Min Cui, Huanchun Chen, Zhen F Fu, Ling Zhao
Previous studies have demonstrated that the lack of interleukin-21 (IL-21) signaling could affect specific antibody induction after rabies vaccination. Here, to further investigate the overexpression of IL-21 on the immunogenicity of rabies virus (RABV), a recombinant RABV expressing murine IL-21, designated as LBNSE-IL21, was constructed and evaluated in a mouse model. It was found that mice immunized with LBNSE-IL21 could substantially increase the number of T follicular helper (Tfh) cells and germinal center (GC) B cells but did not enhance dendritic cell (DC) activation...
October 25, 2016: Journal of General Virology
https://www.readbyqxmd.com/read/27900450/il-9-and-th9-in-parasite-immunity
#16
REVIEW
P Licona-Limón, A Arias-Rojas, E Olguín-Martínez
Interleukin-9 is a cytokine classically related to type 2 immune responses whose cellular identity has been recently reevaluated to identify a new specialized T helper subset called Th9 and an innate source referred as innate lymphoid cell type 2. Over the past years, IL-9 has been associated with allergic responses, tumor immunology, and autoimmunity; however, in this review, we will specifically focus on the role of IL-9 and Th9 cells in the context of parasitic infections. We will summarize and discuss all the evidence relating IL-9 expression and function in parasitic infections with a particular emphasis in helminth infections, an important health issue in developing countries; we will also provide a general description and classification of parasites, the immune response and cellular compartments activated in this context, and its implications and future directions towards a complete understanding of this interesting new T helper subset and its potential therapeutic use...
November 29, 2016: Seminars in Immunopathology
https://www.readbyqxmd.com/read/27900412/demethyleneberberine-alleviates-inflammatory-bowel-disease-in-mice-through-regulating-nf-%C3%AE%C2%BAb-signaling-and-t-helper-cell-homeostasis
#17
Ying-Ying Chen, Rui-Yan Li, Mei-Jing Shi, Ya-Xing Zhao, Yan Yan, Xin-Xin Xu, Miao Zhang, Xiao-Tong Zhao, Yu-Bin Zhang
OBJECTIVE: The activation of NF-κB signaling and unbalance of T-helper (Th) cells have been reported to play a key role in the pathogenesis of colitis. Cortex Phellodendri Chinensis (CPC) is commonly used to treat inflammation and diarrhea. Demethyleneberberine (DMB), a component of CPC, was reported to treat alcoholic liver disease as a novel natural mitochondria-targeted antioxidant in our previous study. In this study, we investigated whether DMB could protect against dextran sulfate sodium (DSS)-induced inflammatory colitis in mice by regulation of NF-κB pathway and Th cells homeostatis...
November 29, 2016: Inflammation Research: Official Journal of the European Histamine Research Society ... [et Al.]
https://www.readbyqxmd.com/read/27899095/effects-of-the-ayurved-siriraj-wattana-recipe-on-functional-and-phenotypic-characterization-of-cytokine-induced-killer-cells-and-dendritic-cells-in-vitro
#18
Adisak Wongkajornsilp, Nuntarak Numchaisermsuk, Khanit Sa-Ngiamsuntorn, Pravit Akarasereenont, Valla Wamanuttajinda, Kanda Kasetsinsombat, Sunisa Duangsa-Ard, Tawee Laohapan, Kittipong Maneechotesuwan
BACKGROUND: Ayurved Siriraj Wattana recipe (AVS073), has been prescribed as tonic, to increase appetite, and for pain relief. It also exhibits antioxidant, anti-inflammatory, immunomodulating and anti-cancer activities. However, the immunomodulatory effects on antigen-presenting cells and effector T cells remained elusive. We thus aimed to study the effects of AVS073 on differentiation, maturation, functions and proportions of CIK cells and monocyte-derived DCs. METHODS: CIK cells and monocyte-derived DCs were treated with AVS073, followed by the assessment of T-helper (Th) phenotypes using real-time RT-PCR and flow cytometry...
November 29, 2016: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/27898464/donor-derived-exosomes-the-trick-behind-the-semidirect-pathway-of-allorecognition
#19
Adrian E Morelli, William Bracamonte-Baran, William J Burlingham
PURPOSE OF REVIEW: The passenger leukocyte hypothesis predicts that after transplantation, donor antigen-presenting cells (APCs) from the graft present donor MHC molecules to directly alloreactive T cells in lymphoid organs. However, in certain transplantation models, recent evidence contradicts this long-standing concept. New findings demonstrate that host, instead of donor, APCs play a prominent role in allosensitization against donor MHC molecules via the semidirect pathway. A similar mechanism operates in development of T-cell split tolerance to noninherited maternal antigens...
November 24, 2016: Current Opinion in Organ Transplantation
https://www.readbyqxmd.com/read/27898346/amp-kinase-promotes-bcl6-expression-in-both-mouse-and-human-t-cells
#20
Markus M Xie, Tohti Amet, Hong Liu, Qigui Yu, Alexander L Dent
The transcription factor Bcl6 is a master regulator of follicular helper T (TFH) cells, and understanding the signaling pathway that induces Bcl6 and TFH cell differentiation is therefore critical. IL-2 produced during T cell activation inhibits Bcl6 expression but how TFH cells evade IL-2 inhibition is not completely understood. Here we show that Bcl6 is highly up-regulated in activated CD4 T cells following glucose deprivation (GD), and this pathway is insensitive to inhibition by IL-2. Similar to GD, the glucose analog 2-deoxyglucose (2DG) inhibits glycolysis, and 2DG induced Bcl6 expression in activated CD4 T cells...
November 26, 2016: Molecular Immunology
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