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Laurence Pellerin, Ping Chen, Silvia Gregori, Gabriela Hernandez-Hoyos, Rosa Bacchetta, Maria Grazia Roncarolo
IL-10 is a potent immunosuppressive cytokine that promotes the differentiation of tolerogenic dendritic cells (DC-10), and the subsequent induction of antigen-specific T regulatory type 1 (Tr1) cells, which suppress immune responses. However, IL-10 acts on multiple cell types and its effects are not solely inhibitory, therefore, limiting its use as immunomodulant. APVO210 is a bispecific fusion protein composed of an anti-CD86 antibody fused with monomeric IL-10 (ADAPTIR™ from Aptevo Therapeutics). APVO210 specifically induces IL-10R signaling in CD86+ antigen-presenting cells, but not in T and B cells...
2018: Frontiers in Immunology
Maurício Barcelos Costa, Emerith Mayra Hungria, Aline Araújo Freitas, Ana Lúcia O M Sousa, Juliano Jampietro, Fernando A Soares, Mariane M A Stefani
Leprosy is a complex chronic, infectious dermato-neurological disease that affects the skin and peripheral nerves especially during immuno-inflammatory episodes known as type 1/T1R and type 2/T2R reactions. This study investigated the in situ expression of CD25+Foxp3+ Treg cells and TGF-β1, IFN-γ, IL-17 in leprosy T1R and T2R. Tregs were evaluated in 114 skin biopsies from 74 leprosy patients: 56 T1R (28-paired reaction-free/reactional biopsies, 28 unpaired T1R), 18 T2R (12 paired reaction-free/reactional biopsies, 6 unpaired T2R)...
2018: PloS One
S Keisin Wang, Linden A Green, Ashley R Gutwein, Bianca Kenyon, Raghu L Motaganahalli, Andres Fajardo, Alok K Gupta, Michael P Murphy
Introduction The protective effect of diabetes mellitus on abdominal aortic aneurysm formation and growth has been repeatedly observed in population studies but continues to be poorly understood. However, recent investigations have suggested that metformin, a staple antihyperglycemic medication, may be independently protective against abdominal aortic aneurysm formation and growth. Therefore, we describe the effect of metformin in abdominal aortic aneurysm and at-risk patients on markers of inflammation, the driver of early abdominal aortic aneurysm formation and growth...
January 1, 2018: Vascular
Yekaterina O Ostapchuk, Yuliya V Perfilyeva, Elena A Kustova, Natalya T Urazalieva, Nazgul A Omarbaeva, Shynar G Talaeva, Nikolai N Belyaev
BACKGROUND: Regulatory T cells (Tregs) play a major role in tumor escape from immunosurveillance by suppressing effector cells. The number of Tregs is increased in tumor sites and peripheral blood of breast cancer patients. However, the data regarding phenotypic and functional heterogeneity of Treg subpopulations in breast cancer are limited. The present study aimed to investigate the number and suppressive potential of Tregs that possess natural naïve-(N nTregs), effector/memory-like (EM nTregs), and Tr1-like phenotypes in breast cancer patients and healthy women...
May 24, 2018: Breast Cancer: the Journal of the Japanese Breast Cancer Society
Julie Mielle, Rachel Audo, Michael Hahne, Laurence Macia, Bernard Combe, Jacques Morel, Claire Daien
Despite growing evidence highlighting the relevance of increasing IL-10-producing B cells (B10+ cells) in autoimmune diseases, their functions in patients are still unknown. The aim of this study was to evaluate the functions of CpG-induced B10+ cells isolated from healthy controls (HC) and rheumatoid arthritis (RA) patients, on naïve T cell differentiation. We demonstrated that CpG-induced B10+ cells from HC drove naïve T cell differentiation toward regulatory T cells (Treg cells) and IL-10-producing T cells (Tr1) through IL-10 secretion and cellular contacts...
2018: Frontiers in Immunology
Alec Pickett, Mika Torkkeli, Tushita Mukhopadhyay, Boregowda Puttaraju, Amrit Laudari, Andreas Lauritzen, Oier Bikondoa, Jakob Kjelstrup-Hansen, Matti Knaapila, Satish Patil, Suchismita Guha
Copolymers based on diketopyrrolopyrrole (DPP) cores have attracted a lot of attention due to their high p-type as well as n-type carrier mobilities in organic field-effect transistors (FETs) and high power conversion efficiencies in solar cell structures. We report the structural and charge transport properties of n-dialkyl side-chain substituted thiophene DPP end-capped with a phenyl group (Ph-TDPP-Ph) in FETs which were fabricated by vacuum deposition and solvent coating. Grazing incidence X-ray diffraction (GIXRD) from bottom-gate, bottom-contact FET architectures were measured with and without biasing...
May 17, 2018: ACS Applied Materials & Interfaces
Esozia Arroabarren, Jorge Alvarez-Garcia, Marta Anda, Montserrat de Prada, Maria Carmen Ponce, Miriam Palacios
OBJECTIVE: Early recognition of symptoms is essential in anaphylaxis management. The Canadian Paediatric Emergency Triage and Acuity Scale prioritizes anaphylaxis to level I or II (resuscitation or emergency). We analyzed the accuracy of pediatric anaphylaxis triage. METHODS: This was a retrospective review of the triage charts (adaptation of the Canadian Paediatric Emergency Triage and Acuity Scale) of 137 children attended for anaphylaxis at our pediatric emergency department...
May 15, 2018: Pediatric Emergency Care
Chelsea L Edwards, Susanna S Ng, Dillon Corvino, Marcela Montes de Oca, Fabian de Labastida Rivera, Katia Nones, Vanessa Lakis, Nicola Waddell, Fiona H Amante, James S McCarthy, Christian R Engwerda
We examined transcriptional changes in CD4+ T cells during blood-stage Plasmodium falciparum infection in individuals without a history of previous parasite exposure. CD4+ T cell CXCL8 gene (encoding IL-8) transcription was identified as an early biomarker of sub-microscopic P. falciparum infection, with predictive power for parasite growth. Following anti-parasitic drug treatment, a CD4+ T cell regulatory phenotype developed. PD1 expression on CD49b+ CD4+ T (putative type I regulatory (Tr1)) cells after drug treatment negatively correlated with earlier parasite growth...
May 11, 2018: Journal of Infectious Diseases
Fatos Dilan Koseoglu Atilla, Basak Ozgen Saydam, Nihat Ali Erarslan, Ayse Gulden Diniz Unlu, Hamiyet Yilmaz Yasar, Muhammet Ozer, Baris Akinci
INTRODUCTION: The American College of Radiology (ACR) has recently proposed a guideline that recommends clinicians to perform thyroid fine-needle aspiration biopsy (FNAB) on the basis of ultrasound features. In this study, we focused on nodules for which no biopsy is recommended by the ACR Thyroid Imaging, Reporting and Data System (TI-RADS) guideline. SUBJECTS AND METHODS: Two-thousand eight-hundred and forty-seven consecutive patients with thyroid nodules who underwent FNAB according to the 2009 American Thyroid Association (ATA) guideline were included...
May 9, 2018: Endocrine
Zhendong Zhu, Jiyun Ye, Yumei Ma, Peng Hua, Yu Huang, Xuemei Fu, Dexuan Li, Maogen Yuan, Zhonghua Xia
T regulatory type 1 (Tr1) cells can promote tolerance and suppress inflammation. Atherosclerosis may be induced by the proinflammatory activation of cells in the vasculature and the immune system. Hence, we wondered whether defects in Tr1 function were a contributing factor to coronary artery disease (CAD). Data showed that the frequency of IL-10+ Tr1 cells was significantly lower in CAD patients than in controls. Compared to healthy controls, Tr1 cells from CAD patients presented lower CTLA-4 but higher PD-1 expression, in addition to lower IL-10 secretion...
May 3, 2018: Human Immunology
Hanna Erdmann, Jochen Behrends, Kristina Ritter, Alexandra Hölscher, Johanna Volz, Ida Rosenkrands, Christoph Hölscher
During Mycobacterium tuberculosis (Mtb) infection, mice lacking the IL-27R exhibit lower bacterial burdens but develop an immunopathological sequelae in comparison to wild-type mice. We here show that this phenotype correlates with an enhanced recruitment of antigen-specific CCR6+ CD4+ T cells and an increased frequency of IL-17A-producing CD4+ T cells. By comparing the outcome of Mtb infection in C57BL/6, IL-27R-deficient and IL-27R/IL-17A-double deficient mice, we observed that both the increased protection and elevated immunopathology are supported by IL-17A...
May 4, 2018: Mucosal Immunology
Bruce R Blazar, Kelli P A MacDonald, Geoffrey R Hill
Current approaches to prevent and treat graft-versus-host disease (GVHD) after stem cell transplantation rely principally on pharmacological immune suppression. Such approaches are limited by drug toxicity, non-specific immune suppression and a requirement for long-term therapy. Our increased understanding of the regulatory cells and molecular pathways involved in limiting pathogenic immune responses opens the opportunity for the use of these cell subsets to prevent and/or GVHD. The theoretical advantages of this approach is permanency of effect, potential for facilitating tissue repair, and induction of tolerance that obviates a need for ongoing drug therapy...
May 4, 2018: Blood
S Keisin Wang, Linden A Green, Ashley R Gutwein, Natalie A Drucker, Raghu L Motaganahalli, Alok K Gupta, Andres Fajardo, Michael P Murphy
BACKGROUND: The pathogenesis driving the formation of abdominal aortic aneurysms continues to be poorly understood. Therefore, we systemically define the cytokine and circulating immune cell environment observed in human abdominal aortic aneurysm compared with risk-factor matched controls. METHODS: From 2015 to 2017, a total of 274 patients donated blood to the Indiana University Center for Aortic Disease. Absolute concentrations of circulating cytokines were determined, using enzyme-linked immunosorbent assays while the expression of circulating immune cell phenotypes were assayed via flow cytometric analysis...
April 28, 2018: Surgery
Michela Comi, Giada Amodio, Silvia Gregori
The prominent role of tolerogenic dendritic cells (tolDCs) in promoting immune tolerance and the development of efficient methods to generate clinical grade products allow the application of tolDCs as cell-based approach to dampen antigen (Ag)-specific T cell responses in autoimmunity and transplantation. Interleukin (IL)-10 potently modulates the differentiation and functions of myeloid cells. Our group contributed to the identification of IL-10 as key factor in inducing a subset of human tolDCs, named dendritic cell (DC)-10, endowed with the ability to spontaneously release IL-10 and induce Ag-specific T regulatory type 1 (Tr1) cells...
2018: Frontiers in Immunology
Tatiana Jofra, Roberta Di Fonte, Giuseppe Galvani, Mirela Kuka, Matteo Iannacone, Manuela Battaglia, Georgia Fousteri
Tr1 cell therapy is considered an emerging approach to improve transplant tolerance and enhance allogeneic graft survival. However, it remains unclear how Tr1 cells promote transplant tolerance and whether they will be safe and stable in the face of an acute viral infection. By employing a mouse model of pancreatic islet transplantation, we report that Tr1 cell therapy promoted transplant tolerance via de novo induction of Tr1 cells in the recipients. Acute viral infection with lymphocytic choriomeningitis virus (LCMV) had no impact on Tr1 cell number and function, neither on the Tr1 cells infused nor on the ones induced, and that was reflected in the robust maintenance of the graft...
April 23, 2018: European Journal of Immunology
Erika Garner-Spitzer, Claudia Seidl-Friedrich, Ines Zwazl, Michael Hofer, Tamar Kinaciyan, Reinhart Jarisch, Karin Stiasny, Gerhard J Zlabinger, Michael Kundi, Ursula Wiedermann
BACKGROUND: Allergic diseases are caused by Th2-driven immune responses and their treatment with specific immunotherapy (SIT) leads to immunomodulation via IL10, TGF-ß and Th1/Tr1 shift. This phase IV, open-label clinical trial investigated whether allergies and SIT treatment influenced immune responses to routine vaccination. METHODS: We studied three groups: 49 allergic patients (allergic group), 21 allergic patients receiving maintenance doses of SIT (SIT group), and 49 non-allergic controls...
May 11, 2018: Vaccine
Brent A Stanfield, Paul J F Rider, John Caskey, Fabio Del Piero, Konstantin G Kousoulas
Herpes simplex virus is a common causative agent of oral and genital diseases. Novel vaccines and therapeutics are needed to combat herpes infections especially after the failure of subunit vaccines in human clinical trials. We have shown that the live-attenuated HSV-1 VC2 vaccine strain is unable to establish latency in vaccinated animals and produces a robust immune response capable of completely protecting mice against lethal vaginal HSV-1 or HSV-2 infections. The guinea pig represents the best small animal model of genital HSV-2 disease...
May 11, 2018: Vaccine
Zongchang Song, Tongxia Zhang, Guang Li, Ying Tang, Yan Luo, Genhua Yu
Gastric cancer is one of the most lethal malignancies worldwide. Chronic Helicobacter pylori (H. pylori) infection can induce an inflammatory response that promotes atrophic gastritis, a preceding event to cancer development. The type 1 regulatory T (Tr1) cells have recently emerged as a critical participant in maintaining self-tolerance. In this study, we examined Tr1 cells in H. pylori infection and gastric cancer development. While H. pylori-uninfected (uninfected) subjects presented low Tr1 frequency in the peripheral blood, H...
June 15, 2018: Experimental Cell Research
Franklin N Tessler, William D Middleton, Edward G Grant
In 2017, the Thyroid Imaging Reporting and Data System (TI-RADS) Committee of the American College of Radiology (ACR) published a white paper that presented a new risk-stratification system for classifying thyroid nodules on the basis of their appearance at ultrasonography (US). In ACR TI-RADS, points in five feature categories are summed to determine a risk level from TR1 to TR5. Recommendations for biopsy or US follow-up are based on the nodule's ACR TI-RADS level and its maximum diameter. The purpose of this article is to offer practical guidance on how to implement and apply ACR TI-RADS based on the authors' experience with the system...
April 2018: Radiology
Hui Gao, Zhuo Dong, Xinkou Gong, Juancong Dong, Yuyu Zhang, Wei Wei, Rui Wang, Shunzi Jin
Exposure to ionizing radiation often induces T helper (Th) cell differentiation, resulting in an imbalance of Th1 and Th2 cellular subtypes, which can affect the efficacy of cancer radiotherapy. The aim of this study was to analyze differential expression of Th1, Th2 and Th3/Type 1 regulatory T cell (Tr1) subtype-related genes and cytokines in mouse thymocytes after high- and low-dose systemic radiation, using functional classification gene arrays and Elisa assays, and to explore the molecular mechanisms underlying radiation's immune effects and their relationship with Th1/Th2 immunity...
March 15, 2018: Journal of Radiation Research
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