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https://www.readbyqxmd.com/read/29453977/amelioration-of-progressive-autoimmune-encephalomyelitis-by-epigenetic-regulation-involves-selective-repression-of-mature-neutrophils-during-the-preclinical-phase
#1
Arathi Jayaraman, Monica Sharma, Bellur Prabhakar, Mark Holterman, Sundararajan Jayaraman
We have recently demonstrated that treatment of NOD mice with the epigenetic drug Trichostatin A (TSA) ameliorated myelin peptide induced progressive experimental autoimmune encephalomyelitis (P-EAE). Protection was accompanied by induction of antigen-specific T-cell tolerance in the periphery and reduced the influx of T cells into the spinal cord. In this investigation, we examined whether the epigenetic drug could impact the innate immune system as well. Whereas the mature (MHC class II + ) CD11b + Ly-6G + neutrophils expanded substantially in the peripheral lymphoid compartment during the preclinical phase, the MHC class II + , CD11b + Ly-6C + mature monocytes increased modestly throughout the disease course...
February 14, 2018: Experimental Neurology
https://www.readbyqxmd.com/read/29442541/the-ophthalmology-surgical-competency-assessment-rubric-oscar-for-anterior-approach-ptosis-surgery
#2
Valerie Juniat, Karl C Golnik, Francesco P Bernardini, Altug Cetinkaya, Aaron Fay, Bipasha Mukherjee, Farzad Pakdel, Brent Skippen, George M Saleh
PURPOSE: The International Council of Ophthalmology (ICO) is currently developing a series of standardized, internationally validated, teaching tools for key ophthalmic surgical procedures called the Ophthalmology Surgical Competency Assessment Rubrics (OSCARs). This study aims to develop an OSCAR for anterior approach ptosis surgery. METHODS: An international panel of content experts, representing Australia, India, Iran, Italy, Turkey, UK, and the USA was established and worked to develop the rubric using a range of online collaboration tools...
February 14, 2018: Orbit
https://www.readbyqxmd.com/read/29426881/activated-t-follicular-helper-like-cells-are-released-into-blood-after-oral-vaccination-and-correlate-with-vaccine-specific-mucosal-b-cell-memory
#3
Ana Cárdeno, Maria K Magnusson, Marianne Quiding-Järbrink, Anna Lundgren
T follicular helper (Tfh)-like cells with potent B-cell helping ability are mobilized into human circulation after parenteral vaccination and are generally held to reflect ongoing germinal center reactions. However, whether mucosal vaccination induces systemic Tfh responses and how such responses may relate to IgA production are unknown. We investigated the frequencies, phenotype and function of circulating Tfh-like CD4+CXCR5+ T cells (cTfh) in adults receiving an oral inactivated enterotoxigenic Escherichia coli vaccine...
February 9, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29409739/expansion-of-circulating-t-follicular-helper-cells-is-associated-with-disease-progression-in-hiv-infected-individuals
#4
Jianhua Lu, Ying Lv, Zhuo Lv, Yi Xu, Yan Huang, Meilan Cui, Huimin Yan
BACKGROUND: T follicular helper (Tfh) cells within germinal centers (GC) of lymphoid tissue play an important role in HIV infection. Recently, circulating Tfh cells have been described, which share phenotypic and functional characteristics with GC Tfh cells. This study aimed to investigate the effect of HIV infection on four circulating Tfh subsets, including CD4+CXCR5+, CD4+CXCR5+ICOS+, CD4+CXCR5+PD-1+, and CD4+CXCR5+ICOS+PD-1+ cells. PATIENTS AND METHODS: Peripheral blood samples were collected from 33 HIV-infected individuals and 21 healthy controls...
February 3, 2018: Journal of Infection and Public Health
https://www.readbyqxmd.com/read/29408339/icos-activation-in-combination-with-electrochemotherapy-generates-effective-anti-cancer-immunological-responses-in-murine-models-of-primary-secondary-and-metastatic-disease
#5
Liam Friel Tremble, Morgan A O'Brien, Patrick F Forde, Declan M Soden
Electrochemotherapy is an evolving therapy which has recently been shown to induce an immunogenic form of cell death. It is hypothesized that the immunogenic cell death induced by electrochemotherapy may compliment the responses seen with anti-cancer immunotherapies. We therefore examined the effect of electrochemotherapy in combination with ICOS activation, which promotes the activity of previously activated T cells. In comparison to either monotherapy which resulted in no curative outcomes in any model, in a CT26 primary tumour 50% of mice were cured, with 100% of cured mice surviving tumour rechallenge...
February 3, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29398449/rhoa-g17v-induces-t-follicular-helper-cell-specification-and-promotes-lymphomagenesis
#6
Jose R Cortes, Alberto Ambesi-Impiombato, Lucile Couronné, S Aidan Quinn, Christine S Kim, Ana C da Silva Almeida, Zachary West, Laura Belver, Marta Sanchez Martin, Laurianne Scourzic, Govind Bhagat, Olivier A Bernard, Adolfo A Ferrando, Teresa Palomero
Angioimmunoblastic T cell lymphoma (AITL) is an aggressive tumor derived from malignant transformation of T follicular helper (Tfh) cells. AITL is characterized by loss-of-function mutations in Ten-Eleven Translocation 2 (TET2) epigenetic tumor suppressor and a highly recurrent mutation (p.Gly17Val) in the RHOA small GTPase. Yet, the specific role of RHOA G17V in AITL remains unknown. Expression of Rhoa G17V in CD4+ T cells induces Tfh cell specification; increased proliferation associated with inducible co-stimulator (ICOS) upregulation and increased phosphoinositide 3-kinase (PI3K) and mitogen-activated protein kinase signaling...
February 1, 2018: Cancer Cell
https://www.readbyqxmd.com/read/29378030/inducible-costimulator-contributes-to-methicillin-resistant-staphylococcus-aureus-pneumonia
#7
Silvia Pires, Rudy Jacquet, Dane Parker
Staphylococcus aureus is a major cause of both community- and healthcare-acquired pneumonias. Inducible costimulator (ICOS) is part of the CD28 family of proteins and is a target for immune checkpoint therapy. We found ICOS highly expressed on activated CD4 cells in response to S. aureus. In the absence of ICOS, mice had improved survival in a pneumonia model with the methicillin-resistant Staphylococcus aureus (MRSA) strain USA300 and significant reductions in bacterial burden in a nonlethal acute pneumonia model...
January 25, 2018: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/29377743/leptin-upregulates-peripheral-cd4-cxcr5-icos-t-cells-via-increased-il-6-in-rheumatoid-arthritis-patients
#8
Miaomiao Wang, Jing Wei, Han Li, Xunli Ouyang, Xiaotong Sun, Yawei Tang, Haifeng Chen, Bing Wang, Xia Li
CD4+CXCR5+ICOS+ T cells, known as Tfh (T Follicular helper) cells, are required for antibody production. Abnormal production and differentiation of Tfh cells are involved in many autoimmune diseases, including rheumatoid arthritis (RA). Leptin has the property of modulating immune system. Here, we explored the effect of leptin on CD4+CXCR5+ICOS+ T cells production in RA patients. Serum leptin levels were measured by enzyme-linked immunosorbent assay (ELISA). Peripheral blood mononuclear cells (PBMC) stimulated with CD3/CD28 were cultured in the presence and absence of leptin and with or without anti-IL-6 receptor (anti-IL-6R), anti-IL-21R, and anti-IL-12R antibody respectively...
January 29, 2018: Journal of Interferon & Cytokine Research
https://www.readbyqxmd.com/read/29368772/transformative-piezoelectric-enhancement-of-p-vdf-trfe-synergistically-driven-by-nanoscale-dimensional-reduction-and-thermal-treatment
#9
G Ico, A Myung, B S Kim, N V Myung, J Nam
Despite the significant potential of organic piezoelectric materials in the electro-mechanical or mechano-electrical applications that require light and flexible material properties, the intrinsically low piezoelectric performance as compared to traditional inorganic materials has limited their full utilization. In this study, we demonstrate that dimensional reduction of poly(vinylidene fluoride trifluoroethylene) (P(VDF-TrFE)) at the nanoscale by electrospinning, combined with an appropriate thermal treatment, induces a transformative enhancement in piezoelectric performance...
January 25, 2018: Nanoscale
https://www.readbyqxmd.com/read/29367462/high-self-reactivity-drives-t-bet-and-potentiates-treg-function-in-tissue-specific-autoimmunity
#10
Maran L Sprouse, Marissa A Scavuzzo, Samuel Blum, Ivan Shevchenko, Thomas Lee, George Makedonas, Malgorzata Borowiak, Matthew L Bettini, Maria Bettini
T cell receptor (TCR) affinity is a critical factor of Treg lineage commitment, but whether self-reactivity is a determining factor in peripheral Treg function remains unknown. Here, we report that a high degree of self-reactivity is crucial for tissue-specific Treg function in autoimmunity. Based on high expression of CD5, we identified a subset of self-reactive Tregs expressing elevated levels of T-bet, GITR, CTLA-4, and ICOS, which imparted significant protection from autoimmune diabetes. We observed that T-bet expression in Tregs, necessary for control of Th1 autoimmunity, could be induced in an IFNγ-independent fashion and, unlike in conventional T cells (Tconv), was strongly correlated with the strength of TCR signaling...
January 25, 2018: JCI Insight
https://www.readbyqxmd.com/read/29361207/blood-t-follicular-regulatory-cells-t-follicular-helper-cells-ratio-marks-ectopic-lymphoid-structure-formation-and-pd-1-icos-t-follicular-helper-cells-indicate-disease-activity-in-primary-sj%C3%A3-gren-s-syndrome
#11
Valter R Fonseca, Vasco C Romão, Ana Agua-Doce, Mara Santos, Dolores López-Presa, Ana Cristina Ferreira, João Eurico Fonseca, Luis Graca
OBJECTIVES: To investigate whether the balance of blood T follicular helper (Tfh) and Foxp3+ T follicular regulatory (Tfr) cells can inform on ectopic lymphoid neogenesis and disease activity in primary Sjögren's syndrome (SS). METHODS: We prospectively recruited 56 patients with clinical suspicion of SS, 16 of which subsequently fulfilled American European Consensus Group primary SS classification criteria and were compared with 16 patients with non-Sjögren sicca syndrome...
January 23, 2018: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/29358281/visualising-the-interaction-of-cd4-t-cells-and-dcs-in-the-evolution-of-inflammatory-arthritis
#12
Catriona T Prendergast, Agapitos Patakas, Shaima Al-Khabouri, Claire L McIntyre, Iain B McInnes, James M Brewer, Paul Garside, Robert A Benson
OBJECTIVES: Successful early intervention in rheumatoid arthritis (RA) with the aim of resetting immunological tolerance requires a clearer understanding of how specificity, cellular kinetics and spatial behaviour shape the evolution of articular T cell responses. We aimed to define initial seeding of articular CD4+ T cell responses in early experimental arthritis, evaluating their dynamic behaviour and interactions with dendritic cells (DCs) in the inflamed articular environment. METHODS: Antigen-induced arthritis was used to model articular inflammation...
January 22, 2018: Annals of the Rheumatic Diseases
https://www.readbyqxmd.com/read/29353472/rapid-and-precise-measurement-of-the-hydrogen-isotope-composition-of-phyllosilicates-by-continuous-flow-oa-icos
#13
John A Mering, Shaun L L Barker
New methodology is presented for analyzing hydrogen isotope ratios (D/H) in phyllosilicate minerals by laser absorption spectroscopy. D/H measurements were carried out using an OA-ICOS instrument operated in a continuous flow configuration. Water was extracted from minerals in a high temperature quartz column and advanced to the analyzer in a dry air carrier gas stream. We report the first D/H measurements by a laser system for serpentine, muscovite, sericite, talc, and biotite. We also measure kaolinite, gypsum, and small volumes of water...
January 20, 2018: Analytical Chemistry
https://www.readbyqxmd.com/read/29352114/binding-of-nufip2-to-roquin-promotes-recognition-and-regulation-of-icos-mrna
#14
Nina Rehage, Elena Davydova, Christine Conrad, Gesine Behrens, Andreas Maiser, Jenny E Stehklein, Sven Brenner, Juliane Klein, Aicha Jeridi, Anne Hoffmann, Eunhae Lee, Umberto Dianzani, Rob Willemsen, Regina Feederle, Kristin Reiche, Jörg Hackermüller, Heinrich Leonhardt, Sonia Sharma, Dierk Niessing, Vigo Heissmeyer
The ubiquitously expressed RNA-binding proteins Roquin-1 and Roquin-2 are essential for appropriate immune cell function and postnatal survival of mice. Roquin proteins repress target mRNAs by recognizing secondary structures in their 3'-UTRs and by inducing mRNA decay. However, it is unknown if other cellular proteins contribute to target control. To identify cofactors of Roquin, we used RNA interference to screen ~1500 genes involved in RNA-binding or mRNA degradation, and identified NUFIP2 as a cofactor of Roquin-induced mRNA decay...
January 19, 2018: Nature Communications
https://www.readbyqxmd.com/read/29343983/does-transcutaneous-electrical-nerve-stimulation-reduce-pain-and-improve-quality-of-life-in-patients-with-idiopathic-chronic-orchialgia-a-randomized-controlled-trial
#15
Sayed A Tantawy, Dalia M Kamel, Walid Kamal Abdelbasset
Background: Chronic orchialgia is defined as testicular pain, which may be either unilateral or bilateral, lasting for more than 3 months. It disturbs a patient's daily activities and quality of life (QoL), inciting the patient to search for treatments to alleviate the pain. It is estimated that 25% of chronic orchialgia cases are idiopathic. Purpose: The purpose of this study was to investigate how effective transcutaneous electrical nerve stimulation (TENS) is in pain reduction and how it consequently affects the QoL in patients with idiopathic chronic orchialgia (ICO)...
2018: Journal of Pain Research
https://www.readbyqxmd.com/read/29322178/early-genetic-diagnosis-of-neurofibromatosis-type-2-from-skin-plaque-plexiform-schwannomas-in-childhood
#16
Elisabeth Castellanos, Adrià Plana, Cristina Carrato, Meritxell Carrió, Inma Rosas, Emilio Amilibia, Francesc Roca-Ribas, Cristina Hostalot, Alicia Castillo, Andrea Ros, Ariadna Quer, Juan Luis Becerra, Hector Salvador, Conxi Lázaro, Ignacio Blanco, Eduard Serra, Isabel Bielsa
Importance: Neurofibromatosis type 2 (NF2) is a devastating genetic condition characterized by the development of multiple tumors of the nervous system. An early diagnosis of individuals with NF2 would facilitate treatment and reduction of disease impact because most severe effects of the disease do not usually develop before adolescence. Little attention has traditionally been paid to dermatological signs in NF2. However, skin plaques are commonly seen in patients with NF2, normally appearing either at birth or early childhood, providing an opportunity for early NF2 detection and testing...
January 10, 2018: JAMA Dermatology
https://www.readbyqxmd.com/read/29321369/enhancing-car-t-cell-persistence-through-icos-and-4-1bb-costimulation
#17
Sonia Guedan, Avery D Posey, Carolyn Shaw, Anna Wing, Tong Da, Prachi R Patel, Shannon E McGettigan, Victoria Casado-Medrano, Omkar U Kawalekar, Mireia Uribe-Herranz, Decheng Song, J Joseph Melenhorst, Simon F Lacey, John Scholler, Brian Keith, Regina M Young, Carl H June
Successful tumor eradication by chimeric antigen receptor-expressing (CAR-expressing) T lymphocytes depends on CAR T cell persistence and effector function. We hypothesized that CD4+ and CD8+ T cells may exhibit distinct persistence and effector phenotypes, depending on the identity of specific intracellular signaling domains (ICDs) used to generate the CAR. First, we demonstrate that the ICOS ICD dramatically enhanced the in vivo persistence of CAR-expressing CD4+ T cells that, in turn, increased the persistence of CD8+ T cells expressing either CD28- or 4-1BB-based CARs...
January 11, 2018: JCI Insight
https://www.readbyqxmd.com/read/29321143/control-of-humoral-response-in-renal-transplantation-by-belatacept-depends-on-a-direct-effect-on-b-cells-and-impaired-t-follicular-helper-b-cell-crosstalk
#18
Claire Leibler, Allan Thiolat, Carole Hénique, Chloé Samson, Caroline Pilon, Marie Tamagne, France Pirenne, Benoit Vingert, José L Cohen, Philippe Grimbert
Generation of de novo donor-specific antibodies (dnDSAs) after renal transplant is recognized as the leading cause of late transplant failure. Hence, the optimal immunosuppressive strategies to limit dnDSA development need to be defined. Recent clinical trials using the novel costimulatory blockade agent CTLA4-Ig (Belatacept) have shown that kidney transplant recipients (KTRs) treated with Belatacept have better graft survival and function and a lower proportion of dnDSAs than control-treated KTRs. Mechanisms involved in the control of humoral responses by Belatacept remain to be investigated...
January 10, 2018: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/29316975/inducible-t-cell-co-stimulators-regulate-the-proliferation-and-invasion-of-human-hepatocellular-carcinoma-hepg2-cells
#19
Yaning Wei, Yanan Wang, Aimin Zang, Yanhong Shang, Zizheng Song, Zhiyu Wang, Yangyang Wang, Hua Yang
BACKGROUND: This study determined the regulatory effects of inducible T-cell co-stimulators (ICOS) in human hepatocellular carcinoma HepG2 cells using a RNA interference (RNAi) technique. METHODS: A RNAi technique was used to knockdown the expression of ICOS. ICOS expression after knockdown was detected as mRNA and protein levels by RT-PCR and Western blot, respectively. A MTT colorimetric assay was used to detect cell proliferation, and the Transwell assay was used to detect cell invasion...
January 9, 2018: Biological Research
https://www.readbyqxmd.com/read/29308314/serum-exosomes-as-predictors-of-clinical-response-to-ipilimumab-in-metastatic-melanoma
#20
Marco Tucci, Anna Passarelli, Francesco Mannavola, Luigia Stefania Stucci, Paolo Antonio Ascierto, Marilena Capone, Gabriele Madonna, Patrizia Lopalco, Francesco Silvestris
Immunotherapy is effective in metastatic melanoma (MM) but most studies failed in discovering a biomarker predictive of clinical response. Exosomes (Exo) from melanoma cells are detectable in sera of MM patients similarly to those produced by immune cells that control the tumor progression. Here, we investigated by flow-cytometry the levels of Exo from both T-cells and dendritic cells (DCs) in 59 patients with MM treated with IPI and the relative expression of PD-1, CD28 and ICOS as well as CD80 and CD86. We found a significant increment of PD-1 and CD28 expression in patients achieving a clinical response reflected by improvement of both PFS and OS...
2018: Oncoimmunology
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