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Helios immunity

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https://www.readbyqxmd.com/read/28401953/overexpression-of-heparanase-enhances-t-lymphocyte-activities-and-intensifies-the-inflammatory-response-in-a-model-of-murine-rheumatoid-arthritis
#1
Andreas Digre, Kailash Singh, Magnus Åbrink, Rogier M Reijmers, Stellan Sandler, Israel Vlodavsky, Jin-Ping Li
Heparanase is an endo-glucuronidase that degrades heparan sulfate chains. The enzyme is expressed at a low level in normal organs; however, elevated expression of heparanase has been detected in several inflammatory conditions, e.g. in the synovial joints of rheumatoid arthritis (RA) patients. Herein, we have applied the model of collagen-induced arthritis (CIA) to transgenic mice overexpressing human heparanase (Hpa-tg) along with wildtype (WT) mice. About 50% of the induced animals developed clinical symptoms, i...
April 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28392428/modulation-of-experimental-arthritis-by-vagal-sensory-and-central-brain-stimulation
#2
Gabriel Shimizu Bassi, Daniel Penteado Martins Dias, Marcelo Franchin, Jhimmy Talbot, Daniel Gustavo Reis, Gustavo Batista Menezes, Jaci Airton Castania, Norberto Garcia-Cairasco, Leonardo Barbosa Moraes Resstel, Helio Cesar Salgado, Fernando Queiróz Cunha, Thiago Mattar Cunha, Luis Ulloa, Alexandre Kanashiro
Articular inflammation is a major clinical burden in multiple inflammatory diseases, especially in rheumatoid arthritis. Biological anti-rheumatic drug therapies are expensive and increase the risk of systemic immunosuppression, infections, and malignancies. Here, we report that vagus nerve stimulation controls arthritic joint inflammation by inducing local regulation of innate immune response. Most of the previous studies of neuromodulation focused on vagal regulation of inflammation via the efferent peripheral pathway toward the viscera...
April 6, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/28388539/preferential-accumulation-of-regulatory-t-cells-with-highly-immunosuppressive-characteristics-in-breast-tumor-microenvironment
#3
Azharuddin Sajid Syed Khaja, Salman M Toor, Haytham El Salhat, Issam Faour, Navid Ul Haq, Bassam R Ali, Eyad Elkord
Immunosuppressive cells such as regulatory T cells (Tregs) have an ambiguous role in breast cancer prognosis, with studies reporting both positive and negative correlations between Treg infiltration and prognosis. This discrepancy could be due to the different immunosuppressive molecules present in these cells. In the present study, we phenotypically characterize different Treg subsets infiltrating the tumor microenvironment (TME), compared to adjacent normal tissue and peripheral blood of primary breast cancer (PBC) patients...
March 25, 2017: Oncotarget
https://www.readbyqxmd.com/read/28301970/disclosing-the-parameters-leading-to-high-productivity-of-retroviral-producer-cells-lines-evaluating-random-versus-targeted-integration
#4
Vanessa S Bandeira, Hélio A Tomás, Evren Alici, Manuel J T Carrondo, Ana S Coroadinha
Gammaretrovirus and lentivirus are the preferred viral vectors to genetically modify T and natural killer cells to be used in immune cell therapies. The transduction efficiency of hematopoietic and T cells is more efficient using gibbon ape leukemia virus (GaLV) pseudotyping. In this context gammaretroviral vector producer cells offer competitive higher titers than transient lentiviral vectors productions. The main aim of this work was to identify the key parameters governing GaLV-pseudotyped gammaretroviral vector productivity in stable producer cells, using a retroviral vector expression cassette enabling positive (facilitating cell enrichment) and negative cell selection (allowing cell elimination)...
April 2017: Human Gene Therapy Methods
https://www.readbyqxmd.com/read/28276457/cd40-signalling-abrogates-induction-of-ror%C3%AE-t-treg-cells-by-intestinal-cd103-dcs-and-causes-fatal-colitis
#5
Christian Barthels, Ana Ogrinc, Verena Steyer, Stefanie Meier, Ferdinand Simon, Maria Wimmer, Andreas Blutke, Tobias Straub, Ursula Zimber-Strobl, Esther Lutgens, Peggy Marconi, Caspar Ohnmacht, Debora Garzetti, Bärbel Stecher, Thomas Brocker
Immune homeostasis in intestinal tissues depends on the generation of regulatory T (Treg) cells. CD103(+) dendritic cells (DCs) acquire microbiota-derived material from the gut lumen for transport to draining lymph nodes and generation of receptor-related orphan γt(+) (RORγt(+)) Helios(-)-induced Treg (iTreg) cells. Here we show CD40-signalling as a microbe-independent signal that can induce migration of CD103(+) DCs from the lamina propria (LP) to the mesenteric lymph nodes. Transgenic mice with constitutive CD11c-specific CD40-signalling have reduced numbers of CD103(+) DCs in LP and a low frequency of RORγt(+)Helios(-) iTreg cells, exacerbated inflammatory Th1/Th17 responses, high titres of microbiota-specific immunoglobulins, dysbiosis and fatal colitis, but no pathology is detected in other tissues...
March 9, 2017: Nature Communications
https://www.readbyqxmd.com/read/28213366/tumor-infiltrating-and-peripheral-blood-t-cell-immunophenotypes-predict-early-relapse-in-localized-clear-cell-renal-cell-carcinoma
#6
Nicolas A Giraldo, Etienne Becht, Yann Vano, Florent Petitprez, Laetitia Lacroix, Pierre Validire, Rafael Sanchez-Salas, Alexandre Ingels, Stephane Marie Oudard, Audrey Moatti, Bénédicte Buttard, Sarah Bourras, Claire Germain, Xavier Cathelineau, Wolf-Herman Fridman, Catherine Sautes-Fridman
PURPOSE: The efficacy of PD-1 Checkpoint Blockade (ChB) as adjuvant therapy in localized clear cell Renal Cell Carcinoma (ccRCC) is currently unknown. The identification of tumor microenvironment (TME) prognostic biomarkers in this setting may help to define which patients could benefit from ChB and to uncover new therapeutic targets. EXPERIMENTAL DESIGN: We performed multiparametric flow cytometry immunophenotypic analysis of T cells isolated from tumor tissue (TIL), adjacent non-malignant renal tissue (RIL) and peripheral blood (PBL), in a cohort of patients (n=40) with localized ccRCC...
February 17, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28211034/infectious-complications-as-the-leading-cause-of-death-after-kidney-transplantation-analysis-of-more-than-10-000-transplants-from-a-single-center
#7
Flávio de Castro Rodrigues Ferreira, Marina Pontello Cristelli, Mayara Ivani Paula, Henrique Proença, Claudia Rosso Felipe, Helio Tedesco-Silva, José Osmar Medina-Pestana
AIM: To identify specific causes of graft failure in a large sample of kidney transplant patients from a middle-income, developing country. METHODS: Retrospective cohort study analyzing all consecutive single kidney transplants (KTs) performed at a single center in Brazil between January 1st 1998 and December 31st 2013. The database closing date was December 31st 2014. RESULTS: Out of 10,400 KTs, there were 1191 (11.45%) deaths with a functioning graft, 40 cases (0...
February 17, 2017: Journal of Nephrology
https://www.readbyqxmd.com/read/28199419/early-immune-responses-and-development-of-pathogenesis-of-avian-infectious-bronchitis-viruses-with-different-virulence-profiles
#8
Cintia Hiromi Okino, Marcos Antônio Zanella Mores, Iara Maria Trevisol, Arlei Coldebella, Hélio José Montassier, Liana Brentano
Avian infectious bronchitis virus (IBV) primarily replicates in epithelial cells of the upper respiratory tract of chickens, inducing both morphological and immune modulatory changes. However, the association between the local immune responses induced by IBV and the mechanisms of pathogenesis has not yet been completely elucidated. This study compared the expression profile of genes related to immune responses in tracheal samples after challenge with two Brazilian field isolates (A and B) of IBV from the same genotype, associating these responses with viral replication and with pathological changes in trachea and kidney...
2017: PloS One
https://www.readbyqxmd.com/read/28104514/increased-foxp3-helios-regulatory-t-cells-and-decreased-acute-graft-versus-host-disease-after-allogeneic-bone-marrow-transplantation-in-patients-receiving-sirolimus-and-rgi-2001-an-activator-of-invariant-natural-killer-t-cells
#9
Yi-Bin Chen, Yvonne A Efebera, Laura Johnston, Edward D Ball, David Avigan, Lazaros J Lekakis, Carlos R Bachier, Paul Martin, Omar Duramad, Yasuyuki Ishii, Semi Han, Yu-Jin Jung, Dana Lee, Lori Kunkel, Robert S Negrin, Jack D Bui
Regulatory T (Treg) cells play a central role in immune tolerance and prevention of aberrant immune responses. Several studies have suggested that the risk of graft-versus-host disease (GVHD) after allogeneic hematopoietic cell transplantation (HCT) can be ameliorated by increasing Tregs. We have developed an approach of in vivo expansion of Tregs with RGI-2001, a novel liposomal formulation of a synthetic derivative of alpha-galactosylceramide, a naturally occurring ligand that binds to CD1 and activates and expands invariant natural killer cells...
April 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/27941965/cd4-cd8-ratio-and-kt-ratio-predict-yellow-fever-vaccine-immunogenicity-in-hiv-infected-patients
#10
Vivian I Avelino-Silva, Karina T Miyaji, Peter W Hunt, Yong Huang, Marisol Simoes, Sheila B Lima, Marcos S Freire, Helio H Caiaffa-Filho, Marisa A Hong, Dayane Alves Costa, Juliana Zanatta C Dias, Natalia B Cerqueira, Anna Shoko Nishiya, Ester Cerdeira Sabino, Ana M Sartori, Esper G Kallas
BACKGROUND: HIV-infected individuals have deficient responses to Yellow Fever vaccine (YFV) and may be at higher risk for adverse events (AE). Chronic immune activation-characterized by low CD4/CD8 ratio or high indoleamine 2,3-dioxygenase-1 (IDO) activity-may influence vaccine response in this population. METHODS: We prospectively assessed AE, viremia by the YFV virus and YF-specific neutralizing antibodies (NAb) in HIV-infected (CD4>350) and -uninfected adults through 1 year after vaccination...
December 2016: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/27812545/low-dose-il-2-selectively-activates-subsets-of-cd4-tregs-and-nk-cells
#11
Masahiro Hirakawa, Tiago Matos, Hongye Liu, John Koreth, Haesook T Kim, Nicole E Paul, Kazuyuki Murase, Jennifer Whangbo, Ana C Alho, Sarah Nikiforow, Corey Cutler, Vincent T Ho, Philippe Armand, Edwin P Alyea, Joseph H Antin, Bruce R Blazar, Joao F Lacerda, Robert J Soiffer, Jerome Ritz
CD4(+) regulatory T cells (CD4Tregs) play a critical role in the maintenance of immune tolerance and prevention of chronic graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation. IL-2 supports the proliferation and survival of CD4Tregs and previous studies have demonstrated that IL-2 induces selective expansion of CD4Tregs and improves clinical manifestations of chronic GVHD. However, mechanisms for selective activation of CD4Tregs and the effects of low-dose IL-2 on other immune cells are not well understood...
November 3, 2016: JCI Insight
https://www.readbyqxmd.com/read/27798682/distinctive-regulatory-t-cells-and-altered-cytokine-profile-locally-in-the-airways-of-young-smokers-with-normal-lung-function
#12
Mahyar Ostadkarampour, Malin Müller, Johan Öckinger, Susanna Kullberg, Anders Lindén, Anders Eklund, Johan Grunewald, Jan Wahlström
Smoking influences the immune system in different ways and, hypothetically, effects on pulmonary effector and regulatory T cells emerge as potentially detrimental. Therefore, we characterized the frequencies and characteristics of CD4+ and CD8+ T cell subsets in the blood and lungs of young tobacco smokers. Bronchoalveolar lavage (BAL) and peripheral blood were obtained from healthy moderate smokers (n = 18; 2-24 pack-years) and never-smokers (n = 15), all with normal lung function. Cells were stimulated ex vivo and key intracellular cytokines (IFNγ, IL-17, IL-10 and TNFα) and transcription factors (Foxp3, T-bet and Helios) were analyzed using flow cytometry...
2016: PloS One
https://www.readbyqxmd.com/read/27769813/current-progress-toward-vaccine-and-passive-immunization-approaches-for-strongyloides-spp
#13
REVIEW
Marcelo Arantes Levenhagen, Hélio Conte, Julia Maria Costa-Cruz
Strongyloides stercoralis is a helminth parasite that can infect millions of people worldwide, particularly in tropical, subtropical and temperate regions with poor sanitation. Several aspects of epidemiology, biology and host-parasite interactions of S. stercoralis have been studied, and substantial knowledge has been acquired; however, very few studies on immunotherapeutic control strategies to prevent infection and disease in humans have been conducted. Therefore, this article reviews the current progress and targets toward vaccine and passive immunization approaches for Strongyloides spp...
October 18, 2016: Immunology Letters
https://www.readbyqxmd.com/read/27622025/regulatory-t-cells-with-multiple-suppressive-and-potentially-pro-tumor-activities-accumulate-in-human-colorectal-cancer
#14
Eleonora Timperi, Ilenia Pacella, Valeria Schinzari, Chiara Focaccetti, Luca Sacco, Francesco Farelli, Roberto Caronna, Gabriella Del Bene, Flavia Longo, Antonio Ciardi, Sergio Morelli, Anna Rita Vestri, Piero Chirletti, Vincenzo Barnaba, Silvia Piconese
Tregs can contribute to tumor progression by suppressing antitumor immunity. Exceptionally, in human colorectal cancer (CRC), Tregs are thought to exert beneficial roles in controlling pro-tumor chronic inflammation. The goal of our study was to characterize CRC-infiltrating Tregs at multiple levels, by phenotypical, molecular and functional evaluation of Tregs from the tumor site, compared to non-tumoral mucosa and peripheral blood of CRC patients. The frequency of Tregs was higher in mucosa than in blood, and further significantly increased in tumor...
July 2016: Oncoimmunology
https://www.readbyqxmd.com/read/27570813/contribution-of-mesenteric-lymph-nodes-and-galt-to-the-intestinal-foxp3-regulatory-t-cell-compartment
#15
Duke Geem, Vu Ngo, Akihito Harusato, Benoit Chassaing, Andrew T Gewirtz, Rodney D Newberry, Timothy L Denning
This study showed that the absence of CCR7 or mesenteric lymph nodes/gut-associated lymphoid tissue did not appreciably impact total intestinal Foxp3+ regulatory T cell representation in the steady-state. However, mesenteric lymph nodes/GALT are required for normal peripherally induced Foxp3+ regulatory T cell differentiation in the small intestine, but not in the large intestine. BACKGROUND & AIMS: Foxp3+ regulatory T cells (Tregs) in the intestine promote immune tolerance to enteric antigens...
May 2016: Cellular and Molecular Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/27333806/tgf-%C3%AE-expressing-mesenchymal-stem-cells-induce-local-tolerance-in-a-rat-liver-transplantation-model-of-acute-rejection
#16
Jincao Tang, Renjie Yang, Ling Lv, Aihua Yao, Liyong Pu, Aihong Yin, Xiangcheng Li, Yue Yu, Scott L Nyberg, Xuehao Wang
Acute rejection is commonly encountered for long-term survival in liver transplant (LT) recipients and may impact their long-term survival if rejection is severe or recurrent. The aim of this study is to examine the therapeutic potential of transforming growth factor (TGF-β)-overexpressing mesenchymal stem cells (MSCs) in inducing a local immunosuppression in liver grafts after transplantation. MSCs were transduced with a lentiviral vector expressing the human TGF-β1 gene; TGF-β1-overexpressing MSCs (designated as TGF/MSCs) were then transfused into the liver grafts via the portal vein of a rat LT model of acute rejection...
June 22, 2016: Stem Cells
https://www.readbyqxmd.com/read/27272688/amniotic-fluid-soluble-form-of-triggering-receptors-expressed-on-myeloid-cells-a-physiologic-constituent-at-term
#17
Natália Prearo Moço, Laura Fernandes Martin, Bruna Ribeiro de Andrade Ramos, Rodrigo Paupério Soares de Camargo, Stephanno Gomes Pereira Sarmento, Karayna Gil Fernandes, Dionísio Chiaratto Filho, Hélio Amante Miot, Márcia Guimarães da Silva
BACKGROUND: Triggering receptors expressed on myeloid cells-1 (TREM-1) are innate immune receptors that mediate inflammatory response. In recent times, the role of these receptors has become the focus of several studies in the gestational context. Evaluation of soluble TREM-1 concentration in normal pregnancy is scarce, and no data are available on the levels of this receptor in the last weeks of normal pregnancy. METHOD: Amniotic fluid (AF) samples were obtained from 77 patients in the last weeks of normal pregnancy during cesarean section, and the soluble form of TREM-1 (sTREM-1) levels determined using specific sandwich enzyme-linked immunosorbent assay kit...
2017: Gynecologic and Obstetric Investigation
https://www.readbyqxmd.com/read/27224512/a-tnfr2-agonist-facilitates-high-purity-expansion-of-human-low-purity-treg-cells
#18
Xuehui He, Sija Landman, Stijn C G Bauland, Juliette van den Dolder, Hans J P M Koenen, Irma Joosten
Regulatory T cells (Treg) are important for immune homeostasis and are considered of great interest for immunotherapy. The paucity of Treg numbers requires the need for ex vivo expansion. Although therapeutic Treg flow-sorting is feasible, most centers aiming at Treg-based therapy focus on magnetic bead isolation of CD4+CD25+ Treg using a good manufacturing practice compliant closed system that achieves lower levels of cell purity. Polyclonal Treg expansion protocols commonly use anti-CD3 plus anti-CD28 monoclonal antibody (mAb) stimulation in the presence of rhIL-2, with or without rapamycin...
2016: PloS One
https://www.readbyqxmd.com/read/27197194/rapalogs-efficacy-relies-on-the-modulation-of-antitumor-t-cell-immunity
#19
Laurent Beziaud, Laura Mansi, Patrice Ravel, Elodie Lauret Marie-Joseph, Caroline Laheurte, Laurie Rangan, Francis Bonnefoy, Jean-René Pallandre, Laura Boullerot, Clémentine Gamonet, Sindy Vrecko, Lise Queiroz, Tristan Maurina, Guillaume Mouillet, Thierry Nguyen Tan Hon, Elsa Curtit, Bernard Royer, Béatrice Gaugler, Jagadeesh Bayry, Eric Tartour, Antoine Thiery-Vuillemin, Xavier Pivot, Christophe Borg, Yann Godet, Olivier Adotévi
The rapalogs everolimus and temsirolimus that inhibit mTOR signaling are used as antiproliferative drugs in several cancers. Here we investigated the influence of rapalogs-mediated immune modulation on their antitumor efficacy. Studies in metastatic renal cell carcinoma patients showed that everolimus promoted high expansion of FoxP3 (+)Helios(+)Ki67(+) regulatory CD4 T cells (Tregs). In these patients, rapalogs strongly enhanced the suppressive functions of Tregs, mainly in a contact-dependent manner. Paradoxically, a concurrent activation of spontaneous tumor-specific Th1 immunity also occurred...
July 15, 2016: Cancer Research
https://www.readbyqxmd.com/read/27185917/instability-of-helios-deficient-tregs-is-associated-with-conversion-to-a-t-effector-phenotype-and-enhanced-antitumor-immunity
#20
Hidetoshi Nakagawa, Jessica M Sido, Edwin E Reyes, Valerie Kiers, Harvey Cantor, Hye-Jung Kim
Expression of the transcription factor Helios by Tregs ensures stable expression of a suppressive and anergic phenotype in the face of intense inflammatory responses, whereas Helios-deficient Tregs display diminished lineage stability, reduced FoxP3 expression, and production of proinflammatory cytokines. Here we report that selective Helios deficiency within CD4 Tregs leads to enhanced antitumor immunity through induction of an unstable phenotype and conversion of intratumoral Tregs into T effector cells within the tumor microenvironment...
May 31, 2016: Proceedings of the National Academy of Sciences of the United States of America
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