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https://www.readbyqxmd.com/read/29046031/-innate-lymphoid-cells-and-their-role-in-immune-response-regulation
#1
Bibiana Patricia Ruiz-Sánchez, David Cruz-Zárate, Iris Estrada-García, Isabel Wong-Baeza
Innate lymphoid cells (ILCs) are lymphocytes lacking antigen recognition receptors and become activated in response to cytokines and through microbe-associated molecular pattern (MAMP) receptors. ILCs are found mainly in mucosal tissues and participate in the immune response against infections and in chronic inflammatory conditions. ILCs are divided in ILC-1, ILC-2 and ILC-3, and these cells have analogue functions to those of immune adaptive response lymphocytes Th1, Th2 and Th17. ILC-1 express T-bet, produce IFNγ, protect against infections with intracellular microorganisms and are related to inflammatory bowel disease immunopathology...
July 2017: Revista Alergia Mexico: Organo Oficial de la Sociedad Mexicana de Alergia e Inmunología, A.C
https://www.readbyqxmd.com/read/29045749/immune-checkpoint-inhibitor-related-myocarditis
#2
Kazuko Tajiri, Kazutaka Aonuma, Ikuo Sekine
Immune checkpoint inhibitors have demonstrated significant clinical benefit in many cancers. The clinical benefit afforded by these treatments can be accompanied by a unique and distinct spectrum of adverse events. Recently, several fatal cases of immune checkpoint inhibitor-related myocarditis were reported. Although its frequency is comparatively lower than that of other immune-related adverse events, myocarditis can lead to circulatory collapse and lethal ventricular arrhythmia. Immune checkpoints, cytotoxic T-lymphocyte antigen 4 (CTLA-4) and programmed cell death protein 1 (PD-1), play important roles in establishing peripheral tolerance to the heart...
October 17, 2017: Japanese Journal of Clinical Oncology
https://www.readbyqxmd.com/read/29045547/safety-of-resuming-anti-pd-1-in-patients-with-immune-related-adverse-events-iraes-during-combined-anti-ctla-4-and-anti-pd1-in-metastatic-melanoma
#3
M H Pollack, A Betof, H Dearden, K Rapazzo, I Valentine, A S Brohl, K K Ancell, G V Long, A M Menzies, Z Eroglu, D B Johnson, A N Shoushtari
Background: Combined CTLA-4 and PD-1 blockade induces high rates of immune-related adverse events (irAEs). The safety of resuming anti-PD-1 in patients who discontinue combination therapy due to irAEs is not known. Patients and Methods: We assessed patients who experienced clinically significant irAEs from combined CTLA-4 and PD-1 blockade leading to treatment discontinuation at four academic centers. We assessed the safety of resuming anti-PD-1 in terms of recurrent and distinct irAEs...
October 11, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29045540/phase-ii-trial-of-pembrolizumab-in-patients-with-platinum-refractory-germ-cell-tumors-a-hoosier-cancer-research-network-study-gu14-206
#4
N Adra, L H Einhorn, S K Althouse, N R Ammakkanavar, D Musapatika, C Albany, D Vaughn, N H Hanna
Background: Despite remarkable results with salvage standard-dose or high-dose chemotherapy about 15% of patients with relapsed germ-cell tumors (GCT) are incurable. Immune checkpoint inhibitors have produced significant remission in multiple tumor types. We report the first study of immunotherapy in patients with GCT. Patients and Methods: Single arm phase 2 trial investigating pembrolizumab 200mg IV Q3weeks until disease progression in patients with relapsed GCT and no curable options...
October 17, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29045253/gut-microbial-diversity-in-hiv-infection-post-combined-antiretroviral-therapy-a-key-target-for-prevention-of-cardiovascular-disease
#5
Mohamed El-Far, Cécile L Tremblay
PURPOSE OF REVIEW: Although the HIV-infected population is living longer and getting older under current treatment regimens, significant challenges arise for health management as the infection is associated with various premature aging phenotypes, particularly increased incidence of cardiovascular diseases (CVDs). Here we review the current understanding of HIV-related gut dysbiosis in association with CVD and advances in clinical trials aiming to restore gut microbial diversity. RECENT FINDING: Identification of a unique signature for gut dysbiosis in HIV infection between different cohorts remains challenging...
October 17, 2017: Current Opinion in HIV and AIDS
https://www.readbyqxmd.com/read/29045159/cracking-the-vaccine-code-in-tuberculosis
#6
Maziar Divangahi, Marcel A Behr
Considerable effort has been devoted to developing a T cell mediated vaccine against tuberculosis (TB).  However, to date, the evidence that this approach can provide protection against Mycobacterium tuberculosis infection has been limited in pre-clinical models and disappointing in a clinical trial. Our fundamental lack of understanding of protective immunity against TB is still the major impediment to vaccine development. In this perspective article, we aim to distinguish the innate immune mechanisms of host-resistance from T cell mediated host-tolerance, and call for novel approaches to be investigated, in the quest for a new TB vaccine...
October 18, 2017: American Journal of Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/29044530/gingival-tissue-an-extrasynovial-source-of-malondialdehyde-acetaldehyde-adducts-citrullinated-and-carbamylated-proteins
#7
R Bright, G M Thiele, J Manavis, T R Mikuls, J B Payne, P M Bartold
BACKGROUND AND OBJECTIVE: Postranslational modification of proteins can lead to the production of autoantibodies and loss of immune tolerance. This process has been hypothesised to be a critical factor in the pathogenesis of rheumatoid arthritis. The objective of this study was to demonstrate that inflamed human gingival tissue provides an extrasynovial source of malondialdehyde-acetaldehyde adducts, citrullinated and carbamylated proteins all of which are considered to be linked to the development of rheumatoid arthritis...
October 17, 2017: Journal of Periodontal Research
https://www.readbyqxmd.com/read/29044496/ncctg-n0879-alliance-a-randomized-phase-2-cooperative-group-trial-of-carboplatin-paclitaxel-and-bevacizumab%C3%A2-%C3%A2-%C3%A2-everolimus-for-metastatic-melanoma
#8
Robert R McWilliams, Jacob B Allred, Jessica A Slostad, Rajini Katipamula, Roxana S Dronca, Kandelaria M Rumilla, Lori A Erickson, Alan H Bryce, Richard W Joseph, Lisa A Kottschade, David M King, John M Leitch, Svetomir N Markovic
BACKGROUND: Despite the success of immune checkpoint and targeted therapy, many patients with melanoma ultimately require further treatment. The combination of carboplatin, paclitaxel, and bevacizumab (CPB) has demonstrated promising activity in a single-arm study. In the current study, the authors performed a randomized phase 2 study to confirm efficacy and to determine whether adding everolimus would increase the activity of the combination. METHODS: Through the North Central Cancer Treatment Group, a total of 149 patients with unresectable AJCC 6th edition stage IV melanoma were randomized from May 2010 to May 2014 to either CPB or CPB with everolimus (CPBE)...
October 17, 2017: Cancer
https://www.readbyqxmd.com/read/29044097/dna-binding-of-the-tet-transactivator-curtails-antigen-induced-lymphocyte-activation-in-mice
#9
Eleonora Ottina, Victor Peperzak, Katia Schoeler, Emma Carrington, Roswitha Sgonc, Marc Pellegrini, Simon Preston, Marco J Herold, Andreas Strasser, Andreas Villunger
The Tet-On/Off system for conditional transgene expression constitutes state-of-the-art technology to study gene function by facilitating inducible expression in a timed and reversible manner. Several studies documented the suitability and versatility of this system to trace lymphocyte fate and to conditionally express oncogenes or silence tumour suppressor genes in vivo. Here, we show that expression of the tetracycline/doxycycline-controlled Tet-transactivator, while tolerated well during development and in immunologically unchallenged animals, impairs the expansion of antigen-stimulated T and B cells and thereby curtails adaptive immune responses in vivo...
October 18, 2017: Nature Communications
https://www.readbyqxmd.com/read/29042997/cd19-cd24-hi-cd38-hi-regulatory-b-cells-are-associated-with-insulin-resistance-in-type-i-hashimoto-s-thyroiditis-in-chinese-females
#10
Min Yang, Changji Du, Yinping Wang, Jun Liu
Hashimoto's thyroiditis (HT) is typically associated with insulin resistance. The aim of the present study was to investigate the role of regulatory B cells (Bregs) in insulin resistance in patients with HT. A total of 52 female patients with type I HT and 35 matched healthy volunteers were enrolled. Demographic and laboratorial data were collected. A 75 g oral glucose tolerance test was performed on each subject. Flow cytometry was performed to evaluate the levels of CD19(+)CD24(hi)CD38(hi) Bregs in peripheral blood...
October 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29041864/targets-of-therapy-in-progressive-ms
#11
Hans Lassmann
Highly effective anti-inflammatory therapies have so far been developed for patients with relapsing/remitting multiple sclerosis, which also show some benefits in the early progressive stage of the disease. However, treatment options for patients, who have entered the progressive phase, are still limited. Disease starts as an inflammatory process, which induces focal demyelinating lesions in the gray and white matter. This stage of the disease dominates in the relapsing phase, extends into the early stages of progressive disease, and can be targeted by current anti-inflammatory treatments...
October 2017: Multiple Sclerosis: Clinical and Laboratory Research
https://www.readbyqxmd.com/read/29039812/molecular-aspects-of-circadian-pharmacology-and-relevance-for-cancer-chronotherapy
#12
REVIEW
Narin Ozturk, Dilek Ozturk, Ibrahim Halil Kavakli, Alper Okyar
The circadian timing system (CTS) controls various biological functions in mammals including xenobiotic metabolism and detoxification, immune functions, cell cycle events, apoptosis and angiogenesis. Although the importance of the CTS is well known in the pharmacology of drugs, it is less appreciated at the clinical level. Genome-wide studies highlighted that the majority of drug target genes are controlled by CTS. This suggests that chronotherapeutic approaches should be taken for many drugs to enhance their effectiveness...
October 17, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29039764/human-chorionic-gonadotropin-as-a-pivotal-endocrine-immune-regulator-initiating-and-preserving-fetal-tolerance
#13
REVIEW
Anne Schumacher
The pregnancy hormone, human chorionic gonadotropin (hCG), is crucially involved in processes such as implantation and placentation, two milestones of pregnancy whose successful progress is a prerequisite for adequate fetal growth. Moreover, hCG determines fetal fate by regulating maternal innate and adaptive immune responses allowing the acceptance of the foreign fetal antigens. As one of the first signals provided by the embryo to its mother, hCG has the potential to regulate very early pregnancy-driven immune responses, allowing the establishment and preservation of fetal tolerance...
October 17, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29039177/-the-involvement-of-galectin-1-in-implantation-and-pregnancy-maintenance-at-the-maternal-fetal-interface
#14
Minyue Tang, Yimin Zhu
As a member of galectins family, galectin-1(Gal-1)is widely expressed in tissues and cells, and participates in a variety of physiological and pathological processes, such as cell adhesion, proliferation, apoptosis and inflammatory reaction. Recently, it has been found that Gal-1 is highly expressed at the maternal-fetal interface and plays important roles in trophoblast cell proliferation, differentiation and invasion, endometrial receptivity, placental angiogenesis and maternal-fetal immune tolerance. In this review, we outline the expression of Gal-1 at the maternal-fetal interface and the involvement of Gal-1 in embryo implantation and pregnancy maintenance, to provide novel insights for the early diagnosis, prognostic assessment and treatment of early pregnancy loss and pregnancy-related diseases...
May 25, 2017: Zhejiang da Xue Xue Bao. Yi Xue Ban, Journal of Zhejiang University. Medical Sciences
https://www.readbyqxmd.com/read/29039048/sclerosing-and-obstructive-cholangiopathy-in-biliary-atresia-mechanisms-and-association-with-biliary-innate-immunity
#15
REVIEW
Kenichi Harada
Biliary atresia (BA) is histologically characterized by a progressive, sclerosing cholangitis and the obstruction of extrahepatic bile ducts. In terms of the etiology and pathogenesis of BA, several viral infections consisting of dsRNA, including Reoviridae, have been implicated. Human biliary epithelial cells (BECs) possess an innate immune system consisting of Toll-like receptors (TLRs). BECs have negative regulatory mechanisms of TLR tolerance to avoid an excessive inflammatory response to lipopolysaccharide (LPS), a TLR4 ligand; however, they lack the tolerance to poly(I:C) (a synthetic analog of viral dsRNA), a TLR3 ligand...
October 16, 2017: Pediatric Surgery International
https://www.readbyqxmd.com/read/29038659/in-silico-prediction-analysis-of-idiotope-driven-t-b-cell-collaboration-in-multiple-sclerosis
#16
Rune A Høglund, Andreas Lossius, Jorunn N Johansen, Jane Homan, Jūratė Šaltytė Benth, Harlan Robins, Bjarne Bogen, Robert D Bremel, Trygve Holmøy
Memory B cells acting as antigen-presenting cells are believed to be important in multiple sclerosis (MS), but the antigen they present remains unknown. We hypothesized that B cells may activate CD4(+) T cells in the central nervous system of MS patients by presenting idiotopes from their own immunoglobulin variable regions on human leukocyte antigen (HLA) class II molecules. Here, we use bioinformatics prediction analysis of B cell immunoglobulin variable regions from 11 MS patients and 6 controls with other inflammatory neurological disorders (OINDs), to assess whether the prerequisites for such idiotope-driven T-B cell collaboration are present...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29038654/cpg-odn-facilitates-effective-intratracheal-immunization-and-recall-of-memory-against-neoantigen-expressing-alveolar-cells
#17
Mathias Riehn, Marcin Cebula, Hansjörg Hauser, Dagmar Wirth
Intrapulmonary immune reactions are impaired by the tolerogenic environment of the lung. This is manifested by the absence of effective endogenous T cell responses upon neoantigen expression. This tolerance is considered to contribute to lung cancer and inefficient immune therapeutic interventions. To investigate the mechanisms contributing to lung tolerance and to overcome these restrictions, we developed a transgenic mouse model with induction of a neoantigen (OVA) exclusively in alveolar type II epithelial cells...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29038537/b-cells-in-type-1-diabetes-mellitus-and-diabetic-kidney-disease
#18
REVIEW
Mia J Smith, Kimber M Simmons, John C Cambier
Type 1 diabetes mellitus (T1DM) is an autoimmune disorder that affects an estimated 30 million people worldwide. It is characterized by the destruction of pancreatic β cells by the immune system, which leads to lifelong dependency on exogenous insulin and imposes an enormous burden on patients and health-care resources. T1DM is also associated with an increased risk of comorbidities, such as cardiovascular disease, retinopathy, and diabetic kidney disease (DKD), further contributing to the burden of this disease...
October 17, 2017: Nature Reviews. Nephrology
https://www.readbyqxmd.com/read/29038463/ncor1-restrains-thymic-negative-selection-by-repressing-bim-expression-to-spare-thymocytes-undergoing-positive-selection
#19
Jianrong Wang, Nanhai He, Na Zhang, Dexian Quan, Shuo Zhang, Caroline Zhang, Ruth T Yu, Annette R Atkins, Ruihong Zhu, Chunhui Yang, Ying Cui, Christopher Liddle, Michael Downes, Hui Xiao, Ye Zheng, Johan Auwerx, Ronald M Evans, Qibin Leng
Thymocytes must pass both positive and negative selections to become mature T cells. Negative selection purges thymocytes whose T-cell receptors (TCR) exhibit high affinity to self-peptide MHC complexes (self pMHC) to avoid autoimmune diseases, while positive selection ensures the survival and maturation of thymocytes whose TCRs display intermediate affinity to self pMHCs for effective immunity, but whether transcriptional regulation helps conserve positively selected thymocytes from being purged by negative selection remains unclear...
October 16, 2017: Nature Communications
https://www.readbyqxmd.com/read/29038460/a-novel-immunohistochemical-score-to-predict-early-mortality-in-acute-myeloid-leukemia-patients-based-on-indoleamine-2-3-dioxygenase-expression
#20
Abhishek Mangaonkar, Ashis Kumar Mondal, Sadanand Fulzule, Chetan Pundkar, Eun Jeong Park, Anand Jillella, Vamsi Kota, Hongyan Xu, Natasha M Savage, Huidong Shi, David Munn, Ravindra Kolhe
Indoleamine 2,3 dioxygenase-1 (IDO-1) is an enzyme in the kynurenine pathway which augments tumor-induced immune tolerance. Previous studies in childhood acute myeloid leukemia (AML) have shown a negative correlation of IDO-1 mRNA expression with outcomes. The aim of our study was to develop a practical and objective immunohistochemical technique to quantify IDO-1 expression on diagnostic bone marrow biopsies of AML patients in order to facilitate its use in routine clinical practice. IDO-1 mRNA was extracted from diagnostic bone marrow specimens from 29 AML patients...
October 16, 2017: Scientific Reports
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