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Immune tolerance

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https://www.readbyqxmd.com/read/28646511/control-of-autoimmune-inflammation-using-liposomes-to-deliver-positive-allosteric-modulators-of-metabotropic-glutamate-receptors
#1
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/28646042/on-the-role-il-4-il-13-heteroreceptor-plays-in-regulation-of-type-1-diabetes
#2
Tobechukwu K Ukah, Alexis N Cattin-Roy, Weirong Chen, Mindy M Miller, Subhasis Barik, Habib Zaghouani
Type 1 diabetes (T1D) manifests when the insulin-producing pancreatic β cells are destroyed as a consequence of an inflammatory process initiated by lymphocytes of the immune system. The NOD mouse develops T1D spontaneously and serves as an animal model for human T1D. The IL-4Rα/IL-13Rα1 heteroreceptor (HR) serves both IL-4 and IL-13 cytokines, which are believed to function as anti-inflammatory cytokines in T1D. However, whether the HR provides a responsive element to environmental (i.e., physiologic) IL-4/IL-13 in the regulation of peripheral tolerance and the development of T1D has yet to be defined...
June 23, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28645365/complexity-of-immune-responses-to-aav-transgene-products-example-of-factor-ix
#3
REVIEW
Roland W Herzog
After two decades of research, in vivo gene transfer with adeno-associated viral (AAV) vectors has now resulted in successful treatments and even cures for several human diseases. However, the potential for immune responses against the therapeutic gene products remains one of the concerns as this approach is broadened to more patients, diverse diseases, and target organs. Immune responses following gene transfer of coagulation factor IX (FIX) for the treatment of the bleeding disorder hemophilia B has been extensively investigated in multiple animal models...
May 29, 2017: Cellular Immunology
https://www.readbyqxmd.com/read/28645296/myd88-dependent-pro-interleukin-1%C3%AE-induction-in-dendritic-cells-exposed-to-food-grade-synthetic-amorphous-silica
#4
Hans Christian Winkler, Julian Kornprobst, Peter Wick, Lea Maria von Moos, Ioannis Trantakis, Elisabeth Maria Schraner, Barbara Bathke, Hubertus Hochrein, Mark Suter, Hanspeter Naegeli
BACKGROUND: Dendritic cells (DCs) are specialized first-line sensors of foreign materials invading the organism. These sentinel cells rely on pattern recognition receptors such as Nod-like or Toll-like receptors (TLRs) to launch immune reactions against pathogens, but also to mediate tolerance to self-antigens and, in the intestinal milieu, to nutrients and commensals. Since inappropriate DC activation contributes to inflammatory diseases and immunopathologies, a key question in the evaluation of orally ingested nanomaterials is whether their contact with DCs in the intestinal mucosa disrupts this delicate homeostatic balance between pathogen defense and tolerance...
June 23, 2017: Particle and Fibre Toxicology
https://www.readbyqxmd.com/read/28643044/pd-1-signaling-and-inhibition-in-aml-and-mds
#5
REVIEW
Faysal Haroun, Sade A Solola, Samah Nassereddine, Imad Tabbara
Acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) are clinically and molecularly heterogeneous clonal myeloid disorders with a poor prognosis especially in the relapsed refractory setting and in patients above the age of 60. While allogeneic hematopoietic stem cell transplantation (ASCT) is a potentially curative approach, high relapse, morbidity, and mortality rates necessitate the development of alternative therapies. Immune checkpoint inhibitors unmask tumoral immune tolerance and have demonstrated efficacy in the treatment of chemotherapy-resistant hematologic and solid malignancies...
June 22, 2017: Annals of Hematology
https://www.readbyqxmd.com/read/28642997/pd-1-and-cancer-molecular-mechanisms-and-polymorphisms
#6
REVIEW
Arash Salmaninejad, Vahid Khoramshahi, Alireza Azani, Ehsan Soltaninejad, Saeed Aslani, Mohammad Reza Zamani, Masoud Zal, Abolfazl Nesaei, Sayed Mostafa Hosseini
The programmed cell death protein 1 (PD-1) is expressed by activated T cells that act as an immunoregulatory molecule, and are responsible for the negative regulation of T cell activation and peripheral tolerance. The PD-1 gene also encodes an inhibitory cell surface receptor involved in the regulation of T cell functions during immune responses/tolerance. Beyond potent inhibitory effects on T cells, PD-1 also has a role in regulating B cell and monocyte responses. An overexpression of PD-1 has been reported to contribute to immune system avoidance in different cancers...
June 22, 2017: Immunogenetics
https://www.readbyqxmd.com/read/28641362/estimating-the-potential-cost-of-a-high-dose-immune-tolerance-induction-iti-therapy-relative-to-the-cost-of-a-combined-therapy-of-a-low-dose-iti-therapy-with-bypassing-agent-prophylaxis
#7
G Kenet, A Oladapo, J D Epstein, C Thompson, A Novack, D J Nugent
INTRODUCTION: The International Immune Tolerance Study (I-ITI) demonstrated comparable success rates between low (FVIII 50 IU/kg/TIW) and high dose (FVIII 200 IU/kg/day) regimens. While costlier, the high dose ITI regimen achieved shorter time-to-treatment success with fewer bleeding episodes compared to the low dose ITI regimen. Adding bypassing agent prophylaxis (BAP) to a low dose ITI regimen may reduce bleeding while still being less costly than high dose ITI. AIM AND METHODS: An economic model was developed to compare high dose ITI to low dose ITI with BAP...
June 22, 2017: Haemophilia: the Official Journal of the World Federation of Hemophilia
https://www.readbyqxmd.com/read/28641100/bruton-s-tyrosine-kinase-btk-as-a-promising-target-in-solid-tumors
#8
REVIEW
J Molina-Cerrillo, T Alonso-Gordoa, P Gajate, E Grande
Bruton's tyrosine kinase (BTK) is a non-receptor intracellular kinase that belongs to the TEC-family tyrosine kinases together with bone marrow-expressed kinase (BMX), redundant-resting lymphocyte kinase (RLK), and IL-2 inducible T-Cell kinase (ITK). All these proteins play a key role in the intracellular signaling of both B and T lymphocytes. Recently, some preclinical data have demonstrated that BTK is present in certain tumor subtypes and in other relevant cells that are contributing to the tumor microenvironment such as dendritic cells, macrophages, myeloid derived suppressor cells and endothelial cells...
June 9, 2017: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/28641031/treatment-options-for-nonalcoholic-steatohepatitis-a-safety-evaluation
#9
Danny Issa, Julia Wattacheril, Arun J Sanyal
Introduction There is an urgent as yet unmet need to develop highly effective and safe therapeutics for nonalcoholic fatty liver disease (NAFLD). The remarkable progress in understanding NAFLD pathogenesis allowed the identification of injury pathways which may be recruited as therapy targets. Areas covered This article reviews the safety and tolerability data of the NAFLD therapies and explains the mechanistic basis for each of the established and investigational drugs. Treatment targets include: weight loss, anti-metabolic agents such as lipid lowering and anti-diabetic drugs, inflammation, fibrosis and others such as targeting gut microbiota, immune modulation and apoptosis...
June 22, 2017: Expert Opinion on Drug Safety
https://www.readbyqxmd.com/read/28640866/diet-induced-adipose-tissue-expansion-is-mitigated-in-mice-with-a-targeted-inactivation-of-mesoderm-specific-transcript-mest
#10
Rea P Anunciado-Koza, Justin Manuel, Randall L Mynatt, Jingying Zhang, Leslie P Kozak, Robert A Koza
Interindividual variation of white adipose tissue (WAT) expression of mesoderm specific transcript (Mest), a paternally-expressed imprinted gene belonging to the α/β-hydrolase fold protein family, becomes apparent among genetically inbred mice fed high fat diet (HFD) and is positively associated with adipose tissue expansion (ATE). To elucidate a role for MEST in ATE, mice were developed with global and adipose tissue inactivation of Mest. Mice with homozygous (MestgKO) and paternal allelic (MestpKO) inactivation of Mest were born at expected Mendelian frequencies, showed no behavioral or physical abnormalities, and did not perturb expression of the Mest locus-derived microRNA miR-335...
2017: PloS One
https://www.readbyqxmd.com/read/28639409/anti-pd-1-antibodies-in-metastatic-uveal-melanoma-a-treatment-option
#11
Carolin Bender, Alexander Enk, Ralf Gutzmer, Jessica C Hassel
Uveal melanomas (UMs) are a rare form of cancer with clinical and pathological characteristics distinct from cutaneous melanomas. Ipilimumab has shown efficacy and safety in the treatment of metastatic UM. This provides a rationale for treatment with other immune checkpoint inhibitors. This is a retrospective review of 15 patients with metastatic UM treated between June 2014 and February 2016, who received treatment with the anti-PD-1 Abs pembrolizumab or nivolumab. Patients were treated at two German university hospitals...
June 21, 2017: Cancer Medicine
https://www.readbyqxmd.com/read/28639391/an-investigation-of-the-relationship-between-recurrent-spontaneous-abortion-and-memory-t-follicular-helper-cells
#12
Xiaorui Luan, Xiaomin Kang, Weiping Li, Qian Dong
PROBLEM: Immune tolerance with respect to a semi-allogeneic fetus plays a key role in the establishment of a pregnancy. Memory T follicular helper (Tfh) cells have a central role in the regulation of the adaptive immune response. Much of our knowledge of memory Tfh cells' function comes from immune-related diseases. However, the true physiological characteristics of memory Tfh cells and their mode of action in pregnancy remain unclear. METHODS OF STUDY: Deciduas and blood were obtained from 25 recurrent spontaneous abortion (RSA) patients undergoing surgical abortion and 19 normal women in early pregnancy undergoing elective termination...
June 21, 2017: American Journal of Reproductive Immunology: AJRI
https://www.readbyqxmd.com/read/28639386/development-of-immune-response-to-tissue-restricted-self-antigens-in-simultaneous-kidney-pancreas-transplant-recipients-with-acute-rejection
#13
Muthukumar Gunasekaran, Neeta Vachharajani, Joseph P Gaut, Thin Thin Maw, Rowena Delos Santos, Surendra Shenoy, William C Chapman, Jason Wellen, Thalachallour Mohanakumar
Simultaneous kidney-pancreas transplantation (SKP Tx) is a treatment for end-stage kidney disease secondary to diabetes mellitus. We investigated the role of immune responses to donor human leukocyte antigens (HLA) and tissue-restricted kidney and pancreas self-antigens (KSAgs and PSAgs, respectively) in SKP Tx recipients (SKP TxRs). Sera collected from 39 SKP TxRs were used to determine de novo Abs specific for KSAgs (collagen-IV, Col-IV; fibronectin, FN) and PSAgs (insulin, islet cells, glutamic acid decarboxylase, and pancreas-associated protein-1) by ELISA...
June 21, 2017: Clinical Transplantation
https://www.readbyqxmd.com/read/28639129/the-inhibition-of-indoleamine-2-3-dioxygenase-accelerates-early-liver-regeneration-in-mice-after-partial-hepatectomy
#14
Hideyuki Ogiso, Hiroyasu Ito, Ayumu Kanbe, Tatsuya Ando, Akira Hara, Masahito Shimizu, Hisataka Moriwaki, Mitsuru Seishima
BACKGROUND AND AIM: The inflammatory response accelerates early liver regeneration after liver injury and resection. Recent studies have demonstrated that indoleamine 2,3-dioxygenase-1 (IDO1) suppresses the activation of inflammatory cells and induces immune tolerance. In this study, we examined the role of IDO1 in liver regeneration after partial hepatectomy (PHx). METHODS: WT or IDO1-knockout (IDO1-KO) mice received 70% PHx. The liver-body weight ratio after PHx was measured and hepatocyte growth was assessed by immunostaining...
June 21, 2017: Digestive Diseases and Sciences
https://www.readbyqxmd.com/read/28638602/b-cell-depleting-therapy-with-rituximab-or-ofatumumab-in-immunoglobulin-a-nephropathy-or-vasculitis-with-nephritis
#15
Sigrid Lundberg, Emelie Westergren, Jessica Smolander, Annette Bruchfeld
BACKGROUND: Approximately 30% of adult patients with immunoglobulin A (IgA) nephropathy (IgAN) or IgA vasculitis with nephritis (IgAVN) develop end-stage renal disease during long-term follow-up. In particular, patients with nephritic-nephrotic syndrome have an increased risk of rapid progression. Conventional immunosuppressive therapy with corticosteroids (CSs) may be insufficient for disease control and is associated with a number of side effects. Rituximab (RTX) has been shown to be well tolerated and effective in a range of glomerular diseases, but there is little information on its therapeutic potential in IgAN...
February 2017: Clinical Kidney Journal
https://www.readbyqxmd.com/read/28638138/immune-regulation-by-oral-tolerance-induces-alternate-activation-of-macrophages-and-reduces-markers-of-plaque-destabilization-in-apob-tm2sgy-ldlr-tm1her-j-mice
#16
Lakshmi Narasimha Thota, Thiruvelselvan Ponnusamy, Sheena Philip, Xinjie Lu, Lakshmi Mundkur
Atherosclerosis is the leading cause for cardiovascular mortality. We determined the effect of multi-antigenic construct expressing three peptides AHC (ApoB100, HSP60 and outer membrane protein of chlamydia pneumonia) in stabilizing advanced atherosclerosis in Apob(tm2Sgy)/Ldlr(tm1Her/J) mice. Atherosclerosis was induced by feeding high fat diet (HFD) to mice for 10 weeks, followed by five oral dosing with purified AHC or ovalbumin on alternate days and continued on HFD for another 10 weeks. Tolerance was associated with significantly higher numbers of regulatory T cells both in aortic sinus and spleen with higher mRNA expression of CTLA4 (3 fold), Foxp3 (1...
June 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28637806/the-pneumococcal-serotype-15c-capsule-is-partially-o-acetylated-and-allows-for-limited-evasion-of-ppv23-elicited-anti-serotype-15b-antibodies
#17
Brady L Spencer, Anukul T Shenoy, Carlos J Orihuela, Moon H Nahm
As a species, Streptococcus pneumoniae (the pneumococcus) utilizes a diverse array of capsular polysaccharides to evade the host. In contrast to large variations in sugar composition and linkage formation, O-acetylation is a subtle capsular modification that nonetheless has a large impact on capsular shielding and recognition of the capsule by vaccine-elicited antibodies. Serotype 15B, which is included in the 23-valent pneumococcal polysaccharide vaccine (PPV23), encodes the putative O-acetyltransferase gene wciZ...
June 21, 2017: Clinical and Vaccine Immunology: CVI
https://www.readbyqxmd.com/read/28635957/itk-signalling-via-the-ras-irf4-pathway-regulates-the-development-and-function-of-tr1-cells
#18
Weishan Huang, Sabrina Solouki, Nicholas Koylass, Song-Guo Zheng, Avery August
Type 1 regulatory T (Tr1) cells differentiate in response to signals engaging the T cell receptor (TCR), express high levels of the immunosuppressive cytokine IL-10, but not Foxp3, and can suppress inflammation and promote immune tolerance. Here we show that ITK, an important modulator of TCR signalling, is required for the TCR-induced development of Tr1 cells in various organs, and in the mucosal system during parasitic and viral infections. ITK kinase activity is required for mouse and human Tr1 cell differentiation...
June 21, 2017: Nature Communications
https://www.readbyqxmd.com/read/28634160/high-throughput-characterization-of-cascade-type-i-e-crispr-guide-efficacy-reveals-unexpected-pam-diversity-and-target-sequence-preferences
#19
Becky Xu Hua Fu, Michael Wainberg, Anshul Kundaje, Andrew Z Fire
Interactions between Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR) RNAs and CRISPR-associated (Cas) proteins form an RNA-guided adaptive immune system in prokaryotes. The adaptive immune system utilizes segments of the genetic material of invasive foreign elements in the CRISPR locus. The loci are transcribed and processed to produce small CRISPR RNAs (crRNAs), with degradation of invading genetic material directed by a combination of complementarity between RNA and DNA and in some cases recognition of adjacent motifs called PAMs (Protospacer Adjacent Motifs)...
June 20, 2017: Genetics
https://www.readbyqxmd.com/read/28633955/the-microbiome-and-transfusion-in-cancer-patients
#20
REVIEW
Hadi Goubran, Jerard Seghatchian, Julia Radosevic, Gaafar Ragab, Thierry Burnouf
Our microbiota is determined by many variables including ABO blood groups. The microbiota is not only confined to the gut and skin but is also recoverable from blood of healthy donors. The microbiota shape our immune system through cross reactivity with antigens, the expression of direct molecular patterns, the release of cytokines, the effects on nutrients and micronutrients and even through an interplay with epigenetics. It is likely, therefore, that a donor's microbiota could alter the antigenicity of blood and its components and potentially contribute to transfusion-related immune modulation [TRIM]...
June 3, 2017: Transfusion and Apheresis Science
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