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https://www.readbyqxmd.com/read/28437578/klrg1-impairs-treg-competitive-fitness-in-the-gut
#1
Holger Meinicke, Anna Bremser, Maria Brack, Klaudia Schrenk, Hanspeter Pircher, Ana Izcue
Immune homeostasis requires the tight, tissue-specific control of the different CD4(+) Foxp3(+) regulatory T cells (Treg) populations. The cadherin-binding inhibitory receptor KLRG1 is expressed by a subpopulation of Treg with GATA3(+) effector phenotype. Although such Treg are important for the immune balance, especially in the gut, the role of KLRG1 in Treg has not been assessed. Using KLRG1 KO mice, we found that KLRG1 deficiency does not affect Treg frequencies in spleen, mesenteric lymph nodes or intestine, or frequencies of GATA3(+) Treg in the gut...
April 24, 2017: Immunology
https://www.readbyqxmd.com/read/28437001/tumor-associated-changes-in-intestinal-epithelial-cells-cause-local-accumulation-of-klrg1-gata3-regulatory-t-cells-in-mice
#2
Holger Meinicke, Anna Bremser, Maria Brack, Paulina Akeus, Claire Pearson, Samuel Bullers, Katrin Hoffmeyer, Marc P Stemmler, Marianne Quiding-Järbrink, Ana Izcue
CD4(+) Foxp3(+) regulatory T cells (Treg) include differentiated populations of effector Treg characterized by the expression of specific transcription factors. Tumors, including intestinal malignancies, often present with local accumulation of Treg that can prevent tumor clearance, but how tumor progression leads to Treg accumulation is incompletely understood. Here using genetically modified mouse models we show that ablation of E-cadherin, a process associated with epithelial to mesenchymal transition (EMT) and tumor progression, promotes the accumulation of intestinal Treg by the specific accumulation of the KLRG1(+) GATA3(+) Treg subset...
April 24, 2017: Immunology
https://www.readbyqxmd.com/read/28430359/sulfur-containing-gaseous-signal-molecules-ion-channels-and-cardiovascular-diseases
#3
REVIEW
Wen Yu, Hongfang Jin, Chaoshu Tang, Junbao Du, Zhiren Zhang
Sulfur-containing gaseous signal molecules including hydrogen sulfide (H2 S) and sulfur dioxide (SO2 ) were previously recognized as toxic gases. However, extensive studies have revealed that they can be generated in the cardiovascular system via a sulfur-containing amino acid metabolic pathway, playing an important part in cardiovascular physiology and pathophysiology. Ion channels are pore-forming membrane proteins present in the membrane of all biological cells; functions include establishing a resting membrane potential and controlling action potentials and other electrical signals by conducting ions across the cell membrane...
April 21, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28430349/prognostic-significance-of-infiltrating-immune-cell-subtypes-in-invasive-ductal-carcinoma-of-the-breast
#4
Yangmei Xu, Suzhen Lan, Qiuhong Zheng
PURPOSE: To explore the correlation between tumor-infiltrating immune cell subsets and breast cancer prognosis. MATERIALS AND METHODS: Specimens of 102 patients with invasive ductal carcinoma of the breast were analyzed for immune-related markers (CD8, CD20, FOXP3 and CD68). The number of positive cells in the 3 most highly stained intratumoral stroma areas of the primary tumor was counted. The mean number was calculated and used to divide patients into 2 groups for each marker (CD8-high/CD8-low, CD20-high/CD20-low, FOXP3-high/FOXP3-low, and CD68-high/CD68-low)...
April 20, 2017: Tumori
https://www.readbyqxmd.com/read/28423590/neutralization-of-interleukin-17-suppresses-allergic-rhinitis-symptoms-by-downregulating-th2-and-th17-responses-and-upregulating-the-treg-response
#5
Zhao Wei Gu, Yun Xiu Wang, Zhi Wei Cao
Allergic rhinitis (AR) has long been considered to predominantly involve the actions of Th2 cells, with relatively small contributions from Th1 cells. In recent years, the discovery of Th17 and regulatory T (Treg) cells has rendered the Th1/Th2 balance paradigm more complex and expanded our understanding of the pathogenesis of AR. IL-17, a key cytokine produced by Th17 cells, is known to induce allergen-specific Th2 cell activation, eosinophil and neutrophil accumulation, and serum IgE production in asthma; all of these features may play important roles in AR...
April 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28423200/cd80cd86-deficiency-disrupts-regulatory-cd4-foxp3-t-cell-homeostasis-and-induces-autoimmune-like-alopecia
#6
Ji-Hyun Bae, Woo-Sung Hwang, Yoo-Jin Jang, Yoon-Hoo Lee, Da-Eun Jang, Jung-Sik Kim, Su-Cheong Yeom
Alopecia areata (AA) is an autoimmune disease that results in spot baldness in humans. Adequate animal models for AA are currently lacking. The objective of this study was to elucidate the mechanism of autoimmune-like alopecia (ALA) in C57BL/6.CD80CD86-deficient (B6.CD80CD86(-/-) ) mice. Incidence and severity of alopecia were analyzed in 58 B6.CD80CD86(-/-) mice by using histological examination, flow cytometry, multiplex enzyme-linked immunosorbent assay, quantitative RT-PCR, and CD25 inhibition test. Both male and female B6...
April 19, 2017: Experimental Dermatology
https://www.readbyqxmd.com/read/28423181/mesenteric-lymph-node-cd11b-cd103-pd-l1-high-dendritic-cells-highly-induce-regulatory-t-cells
#7
Aya Shiokawa, Ryutaro Kotaki, Tomohiro Takano, Haruyo Nakajima-Adachi, Satoshi Hachimura
Dendritic cells (DCs) in mesenteric lymph nodes (MLNs) induce Foxp3(+) regulatory T cells to regulate immune responses to beneficial or non-harmful agents in the intestine, such as commensal bacteria and foods. Several studies in MLN DCs have revealed that CD103(+) DC subset highly induces regulatory T cells, and another study has reported that MLN DCs from PD-L1-deficient mice could not induce regulatory T cells. Thus, the present study investigated expression of these molecules on MLN CD11c(+) cells. Four distinct subsets expressing CD103 and/or PD-L1 were identified, namely CD11b(+) CD103(+) PD-L1(High) , CD11b(-) CD103(+) PD-L1(High) , CD11b(-) CD103(+) PD-L1(Low) , and CD11b(+) CD103(-) PD-L1(Int...
April 19, 2017: Immunology
https://www.readbyqxmd.com/read/28422316/regulatory-t-cells-tolerance-induction-in-solid-organ-transplantation
#8
REVIEW
Trishan Vaikunthanathan, Niloufar Safinia, Dominic Boardman, Robert I Lechler, Giovanna Lombardi
The concept of regulatory T cell (Treg) therapy in transplantation is now a reality. Significant advances in science and technology have enabled us to isolate human Tregs, expand them to clinically relevant numbers and infuse them into human transplant recipients. With several Phase I/II trials underway investigating Treg safety and efficacy it is now more crucial than ever to understand their complex biology. However, our journey is by no means complete, results from these trials will undoubtedly provoke both further knowledge and enquiry, which, alongside evolving science will continue to drive the optimization of Treg therapy in the pursuit of transplantation tolerance...
April 19, 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/28420863/changes-of-systemic-immune-response-after-stereotactic-ablative-radiotherapy-sabr-first-results-of-a-prospective-study-in-early-lung-cancer-patients
#9
Jacek Rutkowski, Tomasz Ślebioda, Zbigniew Kmieć, Renata Zaucha
INTRODUCTION    Among all lung tumors non-small cell lung cancer (NSCLC) is the most common. Conventional conservative treatment in medically inoperable patients with early stage NSCLC has a poor outcome. To improve treatment efficacy stereotactic ablative radiotherapy (SABR) has been developed to enable the delivery of high-dose radiation to the tumor.  OBJECTIVES    This prospective study was conducted to confirm the hypothesis that a sudden death of cancer cells after SABR may lead to systemic immune response changes...
April 18, 2017: Polish Archives of Internal Medicine
https://www.readbyqxmd.com/read/28420440/immune-response-after-autologous-hematopoietic-stem-cell-transplantation-in-type-1-diabetes-mellitus
#10
Lei Ye, Li Li, Bing Wan, Minglan Yang, Jie Hong, Weiqiong Gu, Weiqing Wang, Guang Ning
BACKGROUND: This study explored the details of the immune response after autologous hematopoietic stem cell transplantation (AHSCT) treatment in type 1 diabetes mellitus. METHODS: Peripheral blood mononuclear cells (PBMCs) from 18 patients with type 1 diabetes mellitus were taken at baseline and 12 months after AHSCT or insulin-only therapy. The lymphocyte proliferation, mRNA expression and secretion of pro-inflammatory and anti-inflammatory cytokines belonging to T-helper type 1 (Th1), T-helper type 17 (Th17) and regulatory T (Treg) cells in PBMC culture supernatants were assessed...
April 18, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28419443/loss-of-natural-killer-t-nkt-cells-promotes-pancreatic-cancer-in-lsl-kras-g12d-mice
#11
Naveena B Janakiram, Altaf Mohammed, Taylor Bryant, Rebekah Ritchie, Nicole Stratton, Lydgia Jackson, Stan Lightfoot, Doris M Benbrook, Adam Asch, Mark L Lang, Chinthalapally V Rao
Role of unique T cell population, Natural Killer T (NKT) cells which have similar functions like NK cells in PC is not yet evaluated. In order to address the regulatory roles of NKT cells on tumor progression through tumor-associated macrophages (TAM) and their production of microsomal prostaglandin E synthase-1 (mPGES-1) and 5-lipoxygenase (5-LOX) in (Kras)-driven pancreatic tumor (KPT) progression, we crossed CD1d(-/-) mice deficient in both iNKT and vNKT cells with the Kras(G12D) mice. Loss of NKT cells significantly increased pancreatic intraepithelial neoplasia lesions [PanINs] and also increased 5-LOX and mPGES-1 expressions in M2 type macrophages and cancer stem like cells in pancreatic tumors...
April 18, 2017: Immunology
https://www.readbyqxmd.com/read/28415601/regulatory-network-of-gata3-in-pediatric-acute-lymphoblastic-leukemia
#12
Qianqian Hou, Fei Liao, Shouyue Zhang, Duyu Zhang, Yan Zhang, Xueyan Zhou, Xuyang Xia, Yuanxin Ye, Hanshuo Yang, Zhaozhi Li, Leiming Wang, Xi Wang, Zhigui Ma, Yiping Zhu, Liang Ouyang, Yuelan Wang, Hui Zhang, Li Yang, Heng Xu, Yang Shu
GATA3 polymorphisms were reported to be significantly associated with susceptibility of pediatric B-lineage acute lymphoblastic leukemia (ALL), by impacting on GATA3 expression. We noticed that ALL-related GATA3 polymorphism located around in the tissue-specific enhancer, and significantly associated with GATA3 expression. Although the regulatory network of GATA3 has been well reported in T cells, the functional status of GATA3 is poorly understood in B-ALL. We thus conducted genome-wide gene expression association analyses to reveal expression associated genes and pathways in nine independent B-ALL patient cohorts...
March 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/28414061/mechanistic-correlates-of-clinical-responses-to-omalizumab-in-the-setting-of-oral-immunotherapy-for-milk-allergy
#13
Pamela A Frischmeyer-Guerrerio, Madhan Masilamani, Wenjuan Gu, Erica Brittain, Robert Wood, Jennifer Kim, Kari Nadeau, Kirsi M Jarvinen, Alexander Grishin, Robert Lindblad, Hugh A Sampson
BACKGROUND: In our recent clinical trial, the addition of omalizumab to oral immunotherapy (OIT) for milk allergy improved safety but no significant clinical benefit was detected. OBJECTIVE: To investigate mechanisms by which omalizumab modulates immunity in the context of OIT, and to identify baseline biomarkers that predict subgroups of patients most likely to benefit from omalizumab. METHODS: Blood was obtained at baseline and multiple time-points during a placebo-controlled trial of OIT for milk allergy where subjects were randomized to receive omalizumab or placebo...
April 13, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28413498/dynamic-variations-of-the-peripheral-blood-immune-cell-subpopulation-in-patients-with-critical-h7n9-swine-origin-influenza-a-virus-infection-a-retrospective-small-scale-study
#14
Cheng Chen, Wei Sun, Jun Chen, Jian-An Huang
H7N9 influenza is a recently emerging infection with a high mortality rate. The aim of the present study was to investigate dynamic fluctuations of peripheral blood immune cell subgroups in patients with critical H7N9 infection. Flow cytometry was used to assess the cells in whole blood samples from 9 cases. With regard to the innate immune system, in the majority of patients, the natural killer (NK) cell counts were similar to those of monocytes, which demonstrated a gradual increase in the progression period and an early increase followed by a reduction during recovery...
April 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28406993/topical-and-systemic-immunoreaction-triggered-by-intravesical-chemotherapy-in-an-n-butyl-n-4-hydroxybutyl-nitorosamine-induced-bladder-cancer-mouse-model
#15
Shunta Hori, Makito Miyake, Yoshihiro Tatsumi, Sayuri Onishi, Yosuke Morizawa, Yasushi Nakai, Nobumichi Tanaka, Kiyohide Fujimoto
Intravesical bacillus Calmette-Guerin (BCG) treatment is the most common therapy to prevent progression and recurrence of non-muscle invasive bladder cancer (NMIBC). Although the immunoreaction elicited by BCG treatment is well documented, those induced by intravesical treatment with chemotherapeutic agents are much less known. We investigated the immunological profiles caused by mitomycin C, gemcitabine, adriamycin and docetaxel in the N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN)-induced orthotopic bladder cancer mouse model...
2017: PloS One
https://www.readbyqxmd.com/read/28405498/cergutuzumab-amunaleukin-cea-il2v-a-cea-targeted-il-2-variant-based-immunocytokine-for-combination-cancer-immunotherapy-overcoming-limitations-of-aldesleukin-and-conventional-il-2-based-immunocytokines
#16
Christian Klein, Inja Waldhauer, Valeria G Nicolini, Anne Freimoser-Grundschober, Tapan Nayak, Danielle J Vugts, Claire Dunn, Marije Bolijn, Jörg Benz, Martine Stihle, Sabine Lang, Michaele Roemmele, Thomas Hofer, Erwin van Puijenbroek, David Wittig, Samuel Moser, Oliver Ast, Peter Brünker, Ingo H Gorr, Sebastian Neumann, Maria Cristina de Vera Mudry, Heather Hinton, Flavio Crameri, Jose Saro, Stefan Evers, Christian Gerdes, Marina Bacac, Guus van Dongen, Ekkehard Moessner, Pablo Umaña
We developed cergutuzumab amunaleukin (CEA-IL2v, RG7813), a novel monomeric CEA-targeted immunocytokine, that comprises a single IL-2 variant (IL2v) moiety with abolished CD25 binding, fused to the C-terminus of a high affinity, bivalent carcinoembryonic antigen (CEA)-specific antibody devoid of Fc-mediated effector functions. Its molecular design aims to (i) avoid preferential activation of regulatory T-cells vs. immune effector cells by removing CD25 binding; (ii) increase the therapeutic index of IL-2 therapy by (a) preferential retention at the tumor by having a lower dissociation rate from CEA-expressing cancer cells vs...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28403240/snovault-and-encoded-a-novel-object-based-storage-system-and-applications-to-encode-metadata
#17
Benjamin C Hitz, Laurence D Rowe, Nikhil R Podduturi, David I Glick, Ulugbek K Baymuradov, Venkat S Malladi, Esther T Chan, Jean M Davidson, Idan Gabdank, Aditi K Narayana, Kathrina C Onate, Jason Hilton, Marcus C Ho, Brian T Lee, Stuart R Miyasato, Timothy R Dreszer, Cricket A Sloan, J Seth Strattan, Forrest Y Tanaka, Eurie L Hong, J Michael Cherry
The Encyclopedia of DNA elements (ENCODE) project is an ongoing collaborative effort to create a comprehensive catalog of functional elements initiated shortly after the completion of the Human Genome Project. The current database exceeds 6500 experiments across more than 450 cell lines and tissues using a wide array of experimental techniques to study the chromatin structure, regulatory and transcriptional landscape of the H. sapiens and M. musculus genomes. All ENCODE experimental data, metadata, and associated computational analyses are submitted to the ENCODE Data Coordination Center (DCC) for validation, tracking, storage, unified processing, and distribution to community resources and the scientific community...
2017: PloS One
https://www.readbyqxmd.com/read/28400428/suppression-of-lymphocyte-functions-by-plasma-exosomes-correlates-with-disease-activity-in-patients-with-head-and-neck-cancer
#18
Sonja Ludwig, Theofanis Floros, Marie-Nicole Theodoraki, Chang-Sook Hong, Edwin K Jackson, Stephan Lang, Theresa L Whiteside
Purpose: Head and neck cancers (HNC) often induce profound immunosuppression which contributes to disease progression and interferes with immune-based therapies. Body fluids of HNC patients are enriched in exosomes potentially engaged in negative regulation of anti-tumor immune responses. The presence and content of exosomes derived from plasma of HNC patients are evaluated for the ability to induce immune dysfunction and influence disease activity. <p>Experimental Design: Exosomes were isolated by size-exclusion chromatography from plasma of 38 HNC patients and 14 healthy donors...
April 11, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28393361/immune-checkpoints-and-their-inhibition-in-cancer-and-infectious-diseases
#19
REVIEW
Lydia Dyck, Kingston H G Mills
The development of chronic infections and cancer is facilitated by a variety of immune subversion mechanisms, such as the production of anti-inflammatory cytokines, induction of regulatory T (Treg) cells, and expression of immune checkpoint molecules, including CTLA-4 and PD-1. CTLA-4, expressed on T cells, interacts with CD80/CD86, thereby limiting T-cell activation and leading to anergy. PD-1 is predominantly expressed on T cells and its interaction with PD-L1 and PD-L2 expressed on antigen-presenting cells (APCs) and tumors sends a negative signal to T cells, which can lead to T-cell exhaustion...
April 9, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28393074/adenovirus-mediated-ccr7-and-btla-overexpression-enhances-immune-tolerance-and-migration-in-immature-dendritic-cells
#20
Haiming Xin, Jinhong Zhu, Hongcheng Miao, Zhenyu Gong, Xiaochen Jiang, Xiaoyan Feng, Yalin Tong
Our previous report revealed that immature dendritic cells (imDCs) with adenovirus-mediated CCR7 overexpression acquired an enhanced migratory ability but also exhibited the lower immune tolerance observed in more mature cells. In the present study, we aimed to investigate whether BTLA overexpression was sufficient to preserve immune tolerance in imDCs with exogenous CCR7 overexpression. Scanning electron microscopy and surface antigens analysis revealed that BTLA overexpression suppressed DC maturation, an effect further potentiated in CCR7 and BTLA cooverexpressing cells...
2017: BioMed Research International
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