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https://www.readbyqxmd.com/read/28428203/tslp-activated-dendritic-cells-induce-human-t-follicular-helper-cell-differentiation-through-ox40-ligand
#1
Lucia Pattarini, Coline Trichot, Sofia Bogiatzi, Maximilien Grandclaudon, Stephan Meller, Zela Keuylian, Melanie Durand, Elisabetta Volpe, Stefania Madonna, Andrea Cavani, Andrea Chiricozzi, Marco Romanelli, Toshiyuki Hori, Alain Hovnanian, Bernhard Homey, Vassili Soumelis
T follicular helper cells (Tfh) are important regulators of humoral responses. Human Tfh polarization pathways have been thus far associated with Th1 and Th17 polarization pathways. How human Tfh cells differentiate in Th2-skewed environments is unknown. We show that thymic stromal lymphopoietin (TSLP)-activated dendritic cells (DCs) promote human Tfh differentiation from naive CD4 T cells. We identified a novel population, distinct from Th2 cells, expressing IL-21 and TNF, suggestive of inflammatory cells...
April 20, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28413428/transcriptomic-evidence-of-a-para-inflammatory-state-in-the-middle-aged-lumbar-spinal-cord
#2
William Galbavy, Yong Lu, Martin Kaczocha, Michelino Puopolo, Lixin Liu, Mario J Rebecchi
BACKGROUND: We have previously reported elevated expression of multiple pro-inflammatory markers in the lumbar spinal cord (LSC) of middle-aged male rats compared to young adults suggesting a para-inflammatory state develops in the LSC by middle age, a time that in humans is associated with the greatest pain prevalence and persistence. The goal of the current study was to examine the transcriptome-wide gene expression differences between young and middle aged LSC. METHODS: Young (3 month) and middle-aged (17 month) naïve Fisher 344 rats (n = 5 per group) were euthanized, perfused with heparinized saline, and the LSC were removed...
2017: Immunity & Ageing: I & A
https://www.readbyqxmd.com/read/28370072/expression-profiling-of-sudanese-visceral-leishmaniasis-patients-pre-and-post-treatment-with-sodium-stibogluconate
#3
Mohamed A M Salih, Michaela Fakiola, Paul A Lyons, Brima M Younis, Ahmed M Musa, Ahmed M Elhassan, Denise Anderson, Genevieve Syn, Muntaser E Ibrahim, Jenefer M Blackwell, Hiba S Mohamed
Visceral leishmaniasis (VL) in Sudan caused by Leishmania donovani is fatal in susceptible individuals if untreated. Treatment with Sodium Stibogluconate (SSG) leads to post kala azar dermal leishmaniasis (PKDL) in 58% of patients. Here Affymetrix microarrays were used to identify genes differentially expressed in lymph nodes (N=9 paired samples) pre- and post-treatment with SSG. Using the Bioconductor package limma, 438 genes from 28,869 post quality-control probe-sets were differentially expressed (Pnominal ≤0...
March 31, 2017: Parasite Immunology
https://www.readbyqxmd.com/read/28369782/immune-checkpoint-proteins-exploring-their-therapeutic-potential-to-regulate-atherosclerosis
#4
REVIEW
A C Foks, J Kuiper
The immune system provides a large diversity of immune checkpoint proteins, which involve both costimulatory and inhibitory proteins. Costimulatory proteins can promote cell survival, cell cycle progression and differentiation to effector and memory cells, whereas inhibitory proteins terminate these processes to halt ongoing inflammation. Immune checkpoint proteins play a pivotal role in atherosclerosis by regulating the activation and proliferation of various immune and non-immune cells, such as T cells, macrophages and platelets...
March 30, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28349869/modulation-of-regulatory-t-cells-by-intranasal-allergen-immunotherapy-in-an-experimental-rat-model-of-airway-allergy
#5
Saibal Moitra, Ankur Datta, Somnath Mondal, Iman Hazra, Sk Md Omar Faruk, Prasanta K Das, Anjan K Basu, Santanu K Tripathi, Swapna Chaudhuri
Allergic airway diseases such as asthma and allergic rhinitis are increasing in prevalence worldwide. The theory of an altered Th1/Th2 balance in allergic diathesis has recently been termed a "procrustean paradigm" as it failed to explain many preclinical findings. Regulatory T cells (Treg) have now been shown to be critical in T-cell homeostasis and in the maintenance of peripheral tolerance to allergens. Allergen specific immunotherapy (SIT) has been shown to induce regulatory T cells in allergic patients...
March 24, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28335888/second-and-third-generation-drugs-for-immuno-oncology-treatment-the-more-the-better
#6
REVIEW
Wolfram C M Dempke, Klaus Fenchel, Peter Uciechowski, Stephen P Dale
Recent success in cancer immunotherapy (anti-CTLA-4, anti-PD1/PD-L1) has confirmed the hypothesis that the immune system can control many cancers across various histologies, in some cases producing durable responses in a way not seen with many small-molecule drugs. However, only less than 25% of all patients do respond to immuno-oncology drugs and several resistance mechanisms have been identified (e.g. T-cell exhaustion, overexpression of caspase-8 and β-catenin, PD-1/PD-L1 gene amplification, MHC-I/II mutations)...
March 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28320444/ox40-signaling-is-involved-in-the-autoactivation-of-cd4-cd28-t-cells-and-contributes-to-the-pathogenesis-of-autoimmune-arthritis
#7
Juean Jiang, Cuiping Liu, Mi Liu, Yu Shen, Xiaohan Hu, Qin Wang, Jian Wu, Min Wu, Qi Fang, Xueguang Zhang
BACKGROUND: CD4(+)CD28(-) T cells exhibit autoreactive potential in autoimmune disorders, including rheumatoid arthritis (RA). It is not well known which costimulator functions as an alternative second signal in the activation of this subset after CD28 expression is downregulated. Tumor necrosis factor receptor superfamily member OX40 is a key costimulator in the activation of T cells. The aim of this study was to investigate the costimulatory effects of OX40 on CD4(+)CD28(-) T cells in autoimmune arthritis...
March 21, 2017: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/28300714/biomarkers-and-immunotherapeutic-targets-in-glioblastoma
#8
REVIEW
Alice L Hung, Tomas Garzon-Muvdi, Michael Lim
Glioblastoma (GBM) is an aggressive central nervous system (CNS) cancer with poor prognosis despite maximal therapy. The recent advent of immunotherapy holds great promise for improving GBM survival and has already made great strides towards changing current management strategies. A diverse set of biomarkers has been implicated as immunotherapeutic targets and prognostic indicators in other cancers. Some of the more extensively studied examples include cytokines (IL-4, IL-13, and TGF-ß), checkpoint molecules (PD-1, CTLA-4, TIM-3, LAG-3, CD137, GITR, OX40), and growth/angiogenesis proteins (endoglin and EGFR)...
March 11, 2017: World Neurosurgery
https://www.readbyqxmd.com/read/28289708/interruption-of-ox40l-signaling-prevents-costimulation-blockade-resistant-allograft-rejection
#9
William H Kitchens, Ying Dong, David V Mathews, Cynthia P Breeden, Elizabeth Strobert, Maria E Fuentes, Christian P Larsen, Mandy L Ford, Andrew B Adams
The potential of costimulation blockade to serve as a novel transplant immunosuppression strategy has been explored for over 20 years, culminating in the recent clinical approval of belatacept for renal transplant patients. Despite improving long-term graft function and survival compared with calcineurin inhibitors, clinical acceptance of belatacept has been hindered by elevated rates of acute rejection. We examined the signaling pathways required to activate costimulation blockade-resistant alloreactive T cells and identified the OX40/OX40L secondary costimulatory pathway as a promising target...
March 9, 2017: JCI Insight
https://www.readbyqxmd.com/read/28283653/antibody-drug-conjugates-bearing-pyrrolobenzodiazepine-or-tubulysin-payloads-are-immunomodulatory-and-synergize-with-multiple-immunotherapies
#10
Jonathan Rios-Doria, Jay Harper, Raymond Rothstein, Leslie Wetzel, Jon Chesebrough, Allison M Marrero, Cui Chen, Patrick Strout, Kathy Mulgrew, Kelly A McGlinchey, Ryan Fleming, Binyam Bezabeh, John Meekin, David Stewart, Maureen Kennedy, Philip Martin, Andrew Buchanan, Nazzareno Dimasi, Emil F Michelotti, Robert E Hollingsworth
Immunogenic cell death (ICD) is the process by which certain cytotoxic drugs induce apoptosis of tumor cells in a manner that stimulates the immune system. In this study, we investigated whether antibody-drug conjugates (ADC) conjugated with pyrrolobenzodiazepine dimer (PBD) or tubulysin payloads induce ICD, modulate the immune microenvironment, and could combine with IO drugs to enhance antitumor activity. We show that these payloads on their own induced an immune response that prevented the growth of tumors following subsequent tumor cell challenge...
March 10, 2017: Cancer Research
https://www.readbyqxmd.com/read/28283419/circulating-gluten-specific-foxp3-cd39-regulatory-t-cells-have-impaired-suppressive-function-in-celiac-disease
#11
Laura Cook, C Mee Ling Munier, Nabila Seddiki, David van Bockel, Noé Ontiveros, Melinda Y Hardy, Jana K Gillies, Megan K Levings, Hugh Reid, Jan Peterson, Jamie Rossjohn, Robert P Anderson, John Zaunders, Jason A Tye-Din, Anthony D Kelleher
BACKGROUND: Celiac disease is a chronic immune-mediated inflammatory disorder of the gut triggered by dietary gluten. Although the effector T-cell response in celiac disease has been well characterized, the role of regulatory T-cells (Tregs) in the loss of tolerance to gluten remains poorly understood. OBJECTIVE: To define if celiac disease patients have a dysfunction or lack of gluten-specific FOXP3(+) Tregs. METHODS: Treated celiac disease patients underwent oral wheat challenge to stimulate re-circulation of gluten-specific T-cells...
March 7, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28265272/enforced-ox40-stimulation-empowers-booster-vaccines-to-induce-effective-cd4-and-cd8-t-cell-responses-against-mouse-cytomegalovirus-infection
#12
Eleni Panagioti, Louis Boon, Ramon Arens, Sjoerd H van der Burg
There is an imperative need for effective preventive vaccines against human cytomegalovirus as it poses a significant threat to the immunologically immature, causing congenital disease, and to the immune compromised including transplant recipients. In this study, we examined the efficacy of synthetic long peptides (SLPs) as a CD4(+) and CD8(+) T cell-eliciting preventive vaccine approach against mouse CMV (MCMV) infection. In addition, the use of agonistic OX40 antibodies to enhance vaccine efficacy was explored...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28241075/the-transcriptome-of-hiv-1-infected-intestinal-cd4-t-cells-exposed-to-enteric-bacteria
#13
Alyson C Yoder, Kejun Guo, Stephanie M Dillon, Tzu Phang, Eric J Lee, Michael S Harper, Karen Helm, John C Kappes, Christina Ochsenbauer, Martin D McCarter, Cara C Wilson, Mario L Santiago
Global transcriptome studies can help pinpoint key cellular pathways exploited by viruses to replicate and cause pathogenesis. Previous data showed that laboratory-adapted HIV-1 triggers significant gene expression changes in CD4+ T cell lines and mitogen-activated CD4+ T cells from peripheral blood. However, HIV-1 primarily targets mucosal compartments during acute infection in vivo. Moreover, early HIV-1 infection causes extensive depletion of CD4+ T cells in the gastrointestinal tract that herald persistent inflammation due to the translocation of enteric microbes to the systemic circulation...
February 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28214951/inhibition-of-jak-stat-pathway-restrains-tslp-activated-dendritic-cells-mediated-inflammatory-t-helper-type-2-cell-response-in-allergic-rhinitis
#14
Zhaohui Shi, Weihong Jiang, Min Wang, Xiaocheng Wang, Xiaoyuan Li, Xiaodong Chen, Li Qiao
Thymic stromal lymphopoietin (TSLP) has recently been implicated as a key molecule for initiating allergic rhinitis (AR) at the cell-dendritic cell (DC) interface. Previous studies demonstrated that TSLP activated DCs to express more OX40 ligand (OX40L), which is associated with the initiation of T helper type 2 (Th2) cell responses. STAT phosphorylation has been reported to be promoted by TSLP. Thus, we investigated if the JAK/STAT pathway inhibitor CYT387 could affect TSLP-DC-mediated Th2 cell response in naive T cell and AR mice model...
February 18, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28194024/regnase-1-a-rapid-response-ribonuclease-regulating-inflammation-and-stress-responses
#15
REVIEW
Renfang Mao, Riyun Yang, Xia Chen, Edward W Harhaj, Xiaoying Wang, Yihui Fan
RNA-binding proteins (RBPs) are central players in post-transcriptional regulation and immune homeostasis. The ribonuclease and RBP Regnase-1 exerts critical roles in both immune cells and non-immune cells. Its expression is rapidly induced under diverse conditions including microbial infections, treatment with inflammatory cytokines and chemical or mechanical stimulation. Regnase-1 activation is transient and is subject to negative feedback mechanisms including proteasome-mediated degradation or mucosa-associated lymphoid tissue 1 (MALT1) mediated cleavage...
February 13, 2017: Cellular & Molecular Immunology
https://www.readbyqxmd.com/read/28132739/the-th2-polarizing-function-of-atopic-interleukin-17-receptor-b-positive-dendritic-cells-up-regulated-by-lipopolysaccharide
#16
Rui Zheng, Feng-Hong Chen, Wen-Xiang Gao, Dan Wang, Qin-Tai Yang, Kai Wang, Yin-Yan Lai, Jie Deng, Li-Jie Jiang, Yue-Qi Sun, Jian-Bo Shi
BACKGROUND: Recent studies suggest that epithelial cell (EC)-derived cytokines contribute to allergic airway disease exacerbation. OBJECTIVE: To confirm our hypothesis that atopic dendritic cells (DCs) are activated to up-regulate the receptors of cytokines that mainly derived from ECs and enhance TH2 responses. METHODS: The expressions of interleukin 17 receptor B (IL-17RB) (IL-25 receptor), membrane-bound ST2 (IL-33 receptor), thymic stromal lymphopoietin receptor (TSLPR), granulocyte-macrophage colony-stimulating factor receptor (GM-CSFR), and several functional markers on CD1c(+) monocyte-derived DCs (mo-DCs) were detected by flow cytometry...
April 2017: Annals of Allergy, Asthma & Immunology
https://www.readbyqxmd.com/read/28092803/ox40-structure-and-function-what-questions-remain
#17
REVIEW
Jane Willoughby, Jordana Griffiths, Ivo Tews, Mark S Cragg
OX40 is a type 1 transmembrane glycoprotein, reported nearly 30 years ago as a cell surface antigen expressed on activated T cells. Since its discovery, it has been validated as a bone fide costimulatory molecule for T cells and member of the TNF receptor family. However, many questions still remain relating to its function on different T cell sub-sets and with recent interest in its utility as a target for antibody-mediated immunotherapy, there is a growing need to gain a better understanding of its biology...
March 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28086903/negative-immune-factors-might-predominate-local-tumor-immune-status-and-promote-carcinogenesis-in-cervical-carcinoma
#18
Minyi Zhao, Yang Li, Xing Wei, Qian Zhang, Hongran Jia, Shimin Quan, Di Cao, Li Wang, Ting Yang, Juan Zhao, Meili Pei, Sijuan Tian, Yang Yu, Yanping Guo, Xiaofeng Yang
BACKGROUND: The disequilibrium of local immune microenvironment is an essential element during tumorigenesis. METHOD: By conducting real-time polymerase chain reaction, we identified the mRNA level of immune factors, FoxP3 (forkhead box protein P3), CCL22/CCR4 (chemokine (C-C motif) ligand 22/CC chemokine receptor 4), OX40L/OX40 (tumor necrosis factor superfamily member 4/tumor necrosis factor receptor superfamily member 4) and Smad3 (SMAD family member 3) in neoplastic foci and its periphery tissues from 30 cases of squamous cervical carcinoma and 20 cases of normal cervix...
January 13, 2017: Virology Journal
https://www.readbyqxmd.com/read/28069723/a-novel-murine-gitr-ligand-fusion-protein-induces-antitumor-activity-as-a-monotherapy-which-is-further-enhanced-in-combination-with-an-ox40-agonist
#19
Rebecca Leyland, Amanda Watkins, Kathy Mulgrew, Nicholas Holoweckyj, Lisa Bamber, Natalie J Tigue, Emily Offer, John Andrews, Li Yan, Stefanie Mullins, Michael D Oberst, Jane Coates Ulrichsen, David A Leinster, Kelly A McGlinchey, Lesley Young, Michelle Morrow, Scott A Hammond, Philip R Mallinder, Athula Herath, Ching Ching Leow, Robert W Wilkinson, Ross Stewart
PURPOSE: To generate and characterize a murine GITR ligand fusion protein (mGITRL-FP) designed to maximize valency and the potential to agonize the GITR receptor for cancer immunotherapy. EXPERIMENTAL DESIGN: The EC50 value of the mGITRL-FP was compared to an anti-GITR antibody in an in vitro agonistic cell based reporter assay. We assessed the impact of dose, schedule and Fc isotype on antitumor activity and T-cell modulation in the CT26 tumor model. The activity of the mGITRL-FP was compared to an agonistic murine OX40L-FP targeting OX40, in CT26 and B16F10-Luc2 tumor models...
January 9, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28053236/cd8-t-cells-that-coexpress-ror%C3%AE-t-and-t-bet-are-functionally-impaired-and-expand-in-patients-with-distal-bile-duct-cancer
#20
Stalin Chellappa, Harald Hugenschmidt, Morten Hagness, Saranya Subramani, Espen Melum, Pål Dag Line, Knut-Jørgen Labori, Gro Wiedswang, Kjetil Taskén, Einar Martin Aandahl
CD8(+) T cells that express retinoic acid-related orphan receptor (ROR)γt (TC17 cells) have been shown to promote procarcinogenic inflammation and contribute to a tolerogenic microenvironment in tumors. We investigated their phenotype and functional properties in relationship to the pathogenesis of human distal bile duct cancer (DBDC). DBDC patients had an elevated level of type 17 immune responses and the frequency of CD8(+)RORγt(+) T cells (TC17 cells) was increased in peripheral blood. The CD8(+)RORγt(+) T cells represented a highly activated subset and produced IL-17A in equal amount as CD4(+)RORγt(+) T cells (TH17 cells)...
January 4, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
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