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Autoimmunity t cell

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https://www.readbyqxmd.com/read/28646772/prevalence-of-immune-related-systemic-adverse-events-in%C3%A2-patients-treated-with-anti-programmed-cell-death-1-anti-programmed-cell-death-ligand-1-agents-a-single-centre-pharmacovigilance-database-analysis
#1
Sébastien Le Burel, Stéphane Champiat, Christine Mateus, Aurélien Marabelle, Jean-Marie Michot, Caroline Robert, Rakiba Belkhir, Jean-Charles Soria, Salim Laghouati, Anne-Laure Voisin, Olivier Fain, Arsène Mékinian, Laetitia Coutte, Tali-Anne Szwebel, Laetitia Dunogeant, Bertrand Lioger, Cécile Luxembourger, Xavier Mariette, Olivier Lambotte
AIM: The growing use of immune checkpoint inhibitors (ICIs) is associated with the occurrence of immune-related adverse events (irAEs). Few data are published on systemic, immunohaematological and rheumatic irAEs. In a pharmacovigilance database analysis, we screened for these irAEs and calculated their prevalence. PATIENTS AND METHODS: Participants were recruited via Registre des Effets Indésirables Sévères des Anticorps Monoclonaux Immunomodulateurs en Cancérologie (REISAMIC)(1) a French registry of grade ≥2 irAEs occurring in ICI-treated patients...
June 21, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28646573/interferon-%C3%AE-regulates-dendritic-cell-activation-and-migration-in-experimental-autoimmune-encephalomyelitis
#2
Leesa M Pennell, Eleanor N Fish
CD11c+ dendritic cells (DCs) exert a critical role as antigen-presenting cells in regulating pathogenic T cells in multiple sclerosis (MS). To determine whether the therapeutic benefit of interferon (IFN)-β treatment for MS is in part influenced by IFN regulation of DC function, we examined the immunophenotype of DCs derived from IFN-β(+/+) and IFN-β(-/-) mice using a myelin oligodendrocyte glycoprotein (MOG) peptide-induced mouse model of MS, experimental autoimmune encephalomyelitis (EAE). Our earlier work identified that IFN-β(-/-) mice exhibit earlier onset and more rapid progression of neurologic impairment compared with IFN-β(+/+) mice...
June 24, 2017: Immunology
https://www.readbyqxmd.com/read/28646511/control-of-autoimmune-inflammation-using-liposomes-to-deliver-positive-allosteric-modulators-of-metabotropic-glutamate-receptors
#3
Joshua M Gammon, Arjun R Adapa, Christopher M Jewell
Multiple sclerosis (MS) is an autoimmune disease where myelin is incorrectly recognized as foreign and attacked by the adaptive immune system. Dendritic cells (DCs) direct adaptive immunity by presenting antigens to T cells, therefore serving as a target for autoimmune therapies. N-Phenyl-7-(hydroxyimino)cyclopropa[b]chromen-1a-carboxamide (PHCCC), a positive allosteric modulator of metabotropic glutamate receptor 4 (mGluR4), can promote regulatory T cells by altering cytokine secretion to bias T cell differentiation...
June 24, 2017: Journal of Biomedical Materials Research. Part A
https://www.readbyqxmd.com/read/28646409/neuroprotective-effects-of-g-csf-administration-in-microglia-mediated-reactive-t-cell-activation-in-vitro
#4
Wei Peng
G-CSF is a growth factor that has known neuroprotective effects in a variety of experimental brain injury models. As both antigen-presenting microglia and reactive T cells are key components in the development and progression of EAE, the aim of this study is to investigate the neuroprotective effects of recombinant human G-CSF, as administered in microglia-mediated reactive T cell assay in vitro. Our results indicate that G-CSF treatment has no apparent effect for the resting un-activated microglia. G-CSF pre-protection of microglia increased protective cytokine IL-4 production and effectively inhibited the productions of NO and other inflammatory mediators (IFN-γ, TNF-α, IL-1β, IL-17, and chemokine MCP-1) after LPS stimulation...
June 23, 2017: Immunologic Research
https://www.readbyqxmd.com/read/28646041/concurrent-ox40-and-cd30-ligand-blockade-abrogates-the-cd4-driven-autoimmunity-associated-with-ctla4-and-pd1-blockade-while-preserving-excellent-anti-cd8-tumor-immunity
#5
Maher G Nawaf, Maria H Ulvmar, David R Withers, Fiona M McConnell, Fabrina M Gaspal, Gwilym J Webb, Nick D Jones, Hideo Yagita, James P Allison, Peter J L Lane
Although strategies that block FOXP3-dependent regulatory T cell function (CTLA4 blockade) and the inhibitory receptor PD1 have shown great promise in promoting antitumor immune responses in humans, their widespread implementation for cancer immunotherapy has been hampered by significant off-target autoimmune side effects that can be lethal. Our work has shown that absence of OX40 and CD30 costimulatory signals prevents CD4 T cell-driven autoimmunity in Foxp3-deficient mice, suggesting a novel way to block these side effects...
June 23, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28646040/il-23-limits-the-production-of-il-2-and-promotes-autoimmunity-in-lupus
#6
Hong Dai, Fan He, George C Tsokos, Vasileios C Kyttaris
The IL-23/IL-17 pathway is important in multiple autoimmune diseases, but its effect on lupus pathology remains unclear, with opposing trials in murine models of the disease. In this study, we show a disease activity-related upregulation of serum IL-23 and IL-23 receptor in patients with systemic lupus erythematosus (SLE) as compared with healthy controls. When added in SLE T cell in vitro cultures, IL-23 induced IL-17 and limited IL-2 production, whereas T follicular helper and double negative (DN) T cells significantly expanded...
June 23, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28645781/immunomodulatory-mechanism-of-bushen-huoxue-recipe-alleviates-cyclophosphamide-induced-diminished-ovarian-reserve-in-mouse-model
#7
Cong Huang, Kunkun Song, Wenwen Ma, Jiahui Ding, Zhuo Chen, Mingmin Zhang
ETHNOPHARMACOLOGICAL RELEVANCE: Bushen Huoxue recipe (BHR) is a Chinese herbal prescription composed of ten herbs and it is widely used for the treatment of diminished ovarian reserve (DOR). This study investigates the potentially beneficial effects and underlying mechanism of BHR on a cyclophosphamide (CTX) induced model of DOR in mice. MATERIALS AND METHODS: Granules of BHR were first subjected to high performance liquid chromatography (HPLC) to determine the exact ingredients within the mixture...
June 20, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28645307/aberrant-intestinal-microbiota-due-to-il-1-receptor-antagonist-deficiency-promotes-il-17-and-tlr4-dependent-arthritis
#8
Rebecca Rogier, Thomas H A Ederveen, Jos Boekhorst, Harm Wopereis, Jose U Scher, Julia Manasson, Sanne J C M Frambach, Jan Knol, Johan Garssen, Peter M van der Kraan, Marije I Koenders, Wim B van den Berg, Sacha A F T van Hijum, Shahla Abdollahi-Roodsaz
BACKGROUND: Perturbation of commensal intestinal microbiota has been associated with several autoimmune diseases. Mice deficient in interleukin-1 receptor antagonist (Il1rn (-/-) mice) spontaneously develop autoimmune arthritis and are susceptible to other autoimmune diseases such as psoriasis, diabetes, and encephalomyelitis; however, the mechanisms of increased susceptibility to these autoimmune phenotypes are poorly understood. We investigated the role of interleukin-1 receptor antagonist (IL-1Ra) in regulation of commensal intestinal microbiota, and assessed the involvement of microbiota subsets and innate and adaptive mucosal immune responses that underlie the development of spontaneous arthritis in Il1rn (-/-) mice...
June 23, 2017: Microbiome
https://www.readbyqxmd.com/read/28642760/interleukin-6-in-allogeneic-stem-cell-transplantation-its-possible-importance-for-immunoregulation-and-as-a-therapeutic-target
#9
REVIEW
Tor Henrik Anderson Tvedt, Elisabeth Ersvaer, Anders Aune Tveita, Øystein Bruserud
Allogeneic stem cell transplantation is associated with a high risk of treatment-related mortality mainly caused by infections and graft-versus-host disease (GVHD). GVHD is characterized by severe immune dysregulation and impaired regeneration of different tissues, i.e., epithelial barriers and the liver. The balance between pro- and anti-inflammatory cytokine influences the risk of GVHD. Interleukin-6 (IL-6) is a cytokine that previously has been associated with pro-inflammatory effects. However, more recent evidence from various autoimmune diseases (e...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28642092/chemokine-ccl17-is-expressed-by-dendritic-cells-in-the-cns-during-experimental-autoimmune-encephalomyelitis-and-promotes-pathogenesis-of-disease
#10
Christina Ruland, Hannes Renken, Ivan Kuzmanov, Arezoo Fattahi Mehr, Kathrin Schwarte, Manuela Cerina, Alexander Herrmann, David-Marian Otte, Andreas Zimmer, Nicholas Schwab, Sven G Meuth, Volker Arolt, Luisa Klotz, Irmgard Förster, Stefanie Scheu, Judith Alferink
The CC chemokine ligand 17 (CCL17) and its cognate CC chemokine receptor 4 (CCR4) are known to control leukocyte migration, maintenance of TH17 cells, and regulatory T cell (Treg) expansion in vivo. In this study we characterized the expression and functional role of CCL17 in the pathogenesis of experimental autoimmune encephalomyelitis (EAE). Using a CCL17/EGFP reporter mouse model, we could show that CCL17 expression in the CNS can be found in a subset of classical dendritic cells (DCs) that immigrate into the CNS during the effector phase of MOG-induced EAE...
June 19, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/28642030/cyclic-mog35-55-ameliorates-clinical-and-neuropathological-features-of-experimental-autoimmune-encephalomyelitis
#11
Athanasios Lourbopoulos, George Deraos, Minos-Timotheos Matsoukas, Olga Touloumi, Aggeliki Giannakopoulou, Hubert Kalbacher, Nikolaos Grigoriadis, Vasso Apostolopoulos, John Matsoukas
EAE is induced to susceptible mice using linear peptides of myelin proteins of the central nervous system. Specific peptide motifs within the peptide-binding groove of the MHC peptide-complex determines the affinity of the peptide in each animal and the consequent T-cell receptor recognition and activation of the cell. Altered peptide ligand (APL) vaccination is a novel approach based on an effort to induce T-cell tolerance or alter cytokine profile from pro-inflammatory to anti-inflammatory. In the present study we synthesized the MOG35-55 peptide and altered its 3-dimensional conformation to make it a cyclic one (c-MOG35-55)...
June 7, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28641926/targeting-the-gm-csf-receptor-for-the-treatment-of-cns-autoimmunity
#12
Igal Ifergan, Todd S Davidson, Hania Kebir, Dan Xu, Daphne Palacios-Macapagal, Jennifer Cann, Jane M Rodgers, Zoe N Hunter, Camille L Pittet, Sara Beddow, Clare A Jones, Alexandre Prat, Matthew A Sleeman, Stephen D Miller
In multiple sclerosis (MS), there is a growing interest in inhibiting the pro-inflammatory effects of granulocyte-macrophage colony-stimulating factor (GM-CSF). We sought to evaluate the therapeutic potential and underlying mechanisms of GM-CSF receptor alpha (Rα) blockade in animal models of MS. We show that GM-CSF signaling inhibition at peak of chronic experimental autoimmune encephalomyelitis (EAE) results in amelioration of disease progression. Similarly, GM-CSF Rα blockade in relapsing-remitting (RR)-EAE model prevented disease relapses and inhibited T cell responses specific for both the inducing and spread myelin peptides, while reducing activation of mDCs and inflammatory monocytes...
June 19, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28641866/t-bet-expressing-b-cells-novel-target-for-autoimmune-therapies
#13
Anatoly V Rubtsov, Philippa Marrack, Kira Rubtsova
Autoimmune diseases affect more than 23.5million Americans. Traditional therapies for autoimmune diseases involve immunosuppressive drugs that globally dampen immune responses or target and kill large populations of normal immune cells. Both approaches lead to severe dysfunction of the immune system increasing the risk of infections and cancer. Therefore, a more targeted approach, modulating only the pathogenic autoimmune response, would be tremendously beneficial for autoimmune patients. However, only some novel targets involved in pathogenic autoimmune response have been discovered and it is likely that more remain, currently unknown...
May 23, 2017: Cellular Immunology
https://www.readbyqxmd.com/read/28641569/a-review-on-defects-of-dendritic-cells-in-common-variable-immunodeficiency
#14
Laleh Sharifi, Naeimeh Tavakolinia, Fatemeh Kiaee, Nima Rezaie, Monireh Mohsenzadegan, Mansoureh Shariat, Reza Yazdani, Abbas Mirshafiey, Asghar Aghamohammadi, Gholamreza Azizi
BACKGROUND AND OBJECTIVES: Common variable immunodeficiency (CVID) is the most important primary that is associated with clinical complications including recurrent infections, malignancy and autoimmune diseases. The genetic cause of CVID is mostly unknown and only a few genetic causes are identified. The various options are proposed for determining the etiology of CVID patients, such as T- and B-cell defects, Toll-like receptors (TLRs) impairments, altered cytokine production as well as blemished dendritic cells (DCs)...
June 13, 2017: Endocrine, Metabolic & Immune Disorders Drug Targets
https://www.readbyqxmd.com/read/28639577/characteristics-of-good-s-syndrome-in-china-a-systematic-review
#15
REVIEW
Jin-Pei Dong, Wen Gao, Gui-Gen Teng, Yu Tian, Hua-Hong Wang
BACKGROUND: Good's syndrome (GS) is a rare disease characterized by thymoma, hypogammaglobulinemia, low or absent B-cells, decreased T-cells, an inverted CD4+/CD8+ T-cell ratio and reduced T-cell mitogen proliferative responses. GS is difficult to diagnose preoperatively due to its rarity and lack of typical symptoms, the characteristics of Chinese GS patients are still lacking. This study aimed to systematically review all the clinical, laboratory, and immunologic findings of reported cases of Chinese patients with GS...
July 5, 2017: Chinese Medical Journal
https://www.readbyqxmd.com/read/28638382/expanding-role-of-t-cells-in-human-autoimmune-diseases-of-the-central-nervous-system
#16
REVIEW
Deepti Pilli, Alicia Zou, Fiona Tea, Russell C Dale, Fabienne Brilot
It is being increasingly recognized that a dysregulation of the immune system plays a vital role in neurological disorders and shapes the treatment of the disease. Aberrant T cell responses, in particular, are key in driving autoimmunity and have been traditionally associated with multiple sclerosis. Yet, it is evident that there are other neurological diseases in which autoreactive T cells have an active role in pathogenesis. In this review, we report on the recent progress in profiling and assessing the functionality of autoreactive T cells in central nervous system (CNS) autoimmune disorders that are currently postulated to be primarily T cell driven...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28638223/clinical-significance-of-changes-in-the-th17-treg-ratio-in-autoimmune-liver-disease
#17
Ting-Ting Feng, Ting Zou, Xin Wang, Wei-Feng Zhao, Ai-Lan Qin
AIM: To investigate the levels, ratios, and clinical significance of T helper 17 (Th17) cells and regulatory T (Treg) cells in the peripheral blood of patients with autoimmune liver disease (AILD). METHODS: Forty-two AILD patients were included in the experimental group (group E), and 11 healthy subjects were recruited as the control group (group C). Flow cytometry was performed to determine the percentages of Th17 and Treg cells in peripheral blood lymphocytes...
June 7, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28637902/tgf-%C3%AE-1-suppresses-il-33-induced-mast-cell-function
#18
Victor S Ndaw, Daniel Abebayehu, Andrew J Spence, Patrick A Paez, E Motunrayo Kolawole, Marcela T Taruselli, Heather L Caslin, Alena P Chumanevich, Anuya Paranjape, Bianca Baker, Brian O Barnstein, Tamara T Haque, Kasalina N Kiwanuka, Carole A Oskeritzian, John J Ryan
TGF-β1 is involved in many pathological conditions, including autoimmune disorders, cancer, and cardiovascular and allergic diseases. We have previously found that TGF-β1 can suppress IgE-mediated mast cell activation of human and mouse mast cells. IL-33 is a member of the IL-1 family capable of inducing mast cell responses and enhancing IgE-mediated activation. In this study, we investigated the effects of TGF-β on IL-33-mediated mast cell activation. Bone marrow-derived mast cells cultured in TGF-β1, β2, or β3 showed reduced IL-33-mediated production of TNF, IL-6, IL-13, and MCP-1 in a concentration-dependent manner...
June 21, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28637895/cd4-cd8%C3%AE-double-positive-t-cells-in-skin-draining-lymph-nodes-respond-to-inflammatory-signals-from-the-skin
#19
Nana H Overgaard, Jazmina L Cruz, Jennifer A Bridge, Hendrik J Nel, Ian H Frazer, Nicole L La Gruta, Antje Blumenthal, Raymond J Steptoe, James W Wells
CD4(+)CD8(+) double-positive (DP), mature, peripheral T cells are readily detectable in a variety of species and tissues. Despite a common association with autoimmune and malignant skin disorders, however, little is understood about their role or function. Herein, we show that DP T cells are readily detectable in the blood, spleen, and peripheral lymph nodes of naïve C57BL/6 mice. DP T cells were also present in Jα18(-/-) and CD1d(-/-) mice, indicating that these cells are not NK-T cells. After skin administration of CASAC adjuvant, but not Quil A adjuvant, both total DP T cells and skin-infiltrating DP T cells increased in number...
June 21, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28637584/decreased-tim-3-expression-of-peripheral-blood-natural-killer-cells-in-patients-with-severe-aplastic-anemia
#20
Tian Zhang, Xin Yuan, Chunyan Liu, Yi Li, Hui Liu, Lijuan Li, Kai Ding, Ting Wang, Honglei Wang, Zonghong Shao, Rong Fu
Severe aplastic anemia (SAA) is an autoimmune disease characterized by severe pancytopenia and bone marrow failure. In our previous studies, we found natural killer (NK) cells were aberrant in SAA patients. T cell immunoglobulin mucin-3 (TIM-3), an important regulator of immunity, is widely detected on NK cells and may contribute as a marker of activation and maturation of NK cells. In this study, we found that SAA untreated patients had lower TIM-3 expression on NK cells and CD56(dim) NK subsets compared with normal controls, and were correlated with the severity of pancytopenia of SAA...
April 24, 2017: Cellular Immunology
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