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https://www.readbyqxmd.com/read/28439004/endocannabinoid-system-acts-as-a-regulator-of-immune-homeostasis-in-the-gut
#1
Nandini Acharya, Sasi Penukonda, Tatiana Shcheglova, Adam T Hagymasi, Sreyashi Basu, Pramod K Srivastava
Endogenous cannabinoids (endocannabinoids) are small molecules biosynthesized from membrane glycerophospholipid. Anandamide (AEA) is an endogenous intestinal cannabinoid that controls appetite and energy balance by engagement of the enteric nervous system through cannabinoid receptors. Here, we uncover a role for AEA and its receptor, cannabinoid receptor 2 (CB2), in the regulation of immune tolerance in the gut and the pancreas. This work demonstrates a major immunological role for an endocannabinoid. The pungent molecule capsaicin (CP) has a similar effect as AEA; however, CP acts by engagement of the vanilloid receptor TRPV1, causing local production of AEA, which acts through CB2...
April 24, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28402167/multiinstitutional-analysis-of-thyroid-nodule-risk-stratification-using-the-american-college-of-radiology-thyroid-imaging-reporting-and-data-system
#2
William D Middleton, Sharlene A Teefey, Carl C Reading, Jill E Langer, Michael D Beland, Margaret M Szabunio, Terry S Desser
OBJECTIVE: Guidelines for managing thyroid nodules are highly dependent on risk stratification based on sonographic findings. The purpose of this study is to evaluate the risk stratification system used by the American College of Radiology Thyroid Imaging Reporting and Data System (TIRADS). MATERIALS AND METHODS: Patients with thyroid nodules who underwent sonography and fine-needle aspiration were enrolled in a multiinstitutional study. The sonographic nodule features evaluated in the study were composition, echogenicity, margins, and echogenic foci...
April 12, 2017: AJR. American Journal of Roentgenology
https://www.readbyqxmd.com/read/28378637/primary-tr1-cells-from-metastatic-melanoma-eliminate-tumor-promoting-macrophages-through-granzyme-b-and-perforin-dependent-mechanisms
#3
Hongxia Yan, Ping Zhang, Xue Kong, Xianglian Hou, Li Zhao, Tianhang Li, Xiaozhou Yuan, Hongjun Fu
In malignant melanoma, tumor-associated macrophages play multiple roles in promoting tumor growth, such as inducing the transformation of melanocytes under ultraviolet irradiation, increasing angiogenesis in melanomas, and suppressing antitumor immunity. Because granzyme B- and perforin-expressing Tr1 cells could specifically eliminate antigen-presenting cells of myeloid origin, we examined whether Tr1 cells in melanoma could eliminate tumor-promoting macrophages and how the interaction between Tr1 cells and macrophages could affect the growth of melanoma cells...
April 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28349869/modulation-of-regulatory-t-cells-by-intranasal-allergen-immunotherapy-in-an-experimental-rat-model-of-airway-allergy
#4
Saibal Moitra, Ankur Datta, Somnath Mondal, Iman Hazra, Sk Md Omar Faruk, Prasanta K Das, Anjan K Basu, Santanu K Tripathi, Swapna Chaudhuri
Allergic airway diseases such as asthma and allergic rhinitis are increasing in prevalence worldwide. The theory of an altered Th1/Th2 balance in allergic diathesis has recently been termed a "procrustean paradigm" as it failed to explain many preclinical findings. Regulatory T cells (Treg) have now been shown to be critical in T-cell homeostasis and in the maintenance of peripheral tolerance to allergens. Allergen specific immunotherapy (SIT) has been shown to induce regulatory T cells in allergic patients...
March 24, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28345074/single-cell-rna-seq-and-computational-analysis-using-temporal-mixture-modelling-resolves-th1-tfh-fate-bifurcation-in-malaria
#5
Tapio Lönnberg, Valentine Svensson, Kylie R James, Daniel Fernandez-Ruiz, Ismail Sebina, Ruddy Montandon, Megan S F Soon, Lily G Fogg, Arya Sheela Nair, Urijah Liligeto, Michael J T Stubbington, Lam-Ha Ly, Frederik Otzen Bagger, Max Zwiessele, Neil D Lawrence, Fernando Souza-Fonseca-Guimaraes, Patrick T Bunn, Christian R Engwerda, William R Heath, Oliver Billker, Oliver Stegle, Ashraful Haque, Sarah A Teichmann
Differentiation of naïve CD4(+) T cells into functionally distinct T helper subsets is crucial for the orchestration of immune responses. Due to extensive heterogeneity and multiple overlapping transcriptional programs in differentiating T cell populations, this process has remained a challenge for systematic dissection in vivo. By using single-cell transcriptomics and computational analysis using a temporal mixtures of Gaussian processes model, termed GPfates, we reconstructed the developmental trajectories of Th1 and Tfh cells during blood-stage Plasmodium infection in mice...
March 3, 2017: Science Immunology
https://www.readbyqxmd.com/read/28320933/activin-a-co-opts-irf4-and-ahr-signaling-to-induce-human-regulatory-t-cells-that-restrain-asthmatic-responses
#6
Sofia Tousa, Maria Semitekolou, Ioannis Morianos, Aggelos Banos, Aikaterini I Trochoutsou, Tess M Brodie, Nikolaos Poulos, Konstantinos Samitas, Maria Kapasa, Dimitris Konstantopoulos, Giannis Paraskevopoulos, Mina Gaga, Catherine M Hawrylowicz, Federica Sallusto, Georgina Xanthou
Type 1 regulatory T (Tr1) cells play a pivotal role in restraining human T-cell responses toward environmental allergens and protecting against allergic diseases. Still, the precise molecular cues that underlie their transcriptional and functional specification remain elusive. Here, we show that the cytokine activin-A instructs the generation of CD4(+) T cells that express the Tr1-cell-associated molecules IL-10, inducible T-Cell costimulator (ICOS), lymphocyte activation gene 3 protein (LAG-3), and CD49b, and exert strongly suppressive functions toward allergic responses induced by naive and in vivo-primed human T helper 2 cells...
April 4, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28265263/genome-sequence-of-desulfurella-amilsii-strain-tr1-and-comparative-genomics-of-desulfurellaceae-family
#7
Anna P Florentino, Alfons J M Stams, Irene Sánchez-Andrea
The acidotolerant sulfur reducer Desulfurella amilsii was isolated from sediments of Tinto River, an extremely acidic environment. Its ability to grow in a broad range of pH and to tolerate certain heavy metals offers potential for metal recovery processes. Here we report its high-quality draft genome sequence and compare it to the available genome sequences of other members of Desulfurellaceae family: D. acetivorans. D. multipotens, Hippea maritima. H. alviniae, H. medeae, and H. jasoniae. For most species, pairwise comparisons for average nucleotide identity (ANI) and in silico DNA-DNA hybridization (DDH) revealed ANI values from 67...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28251482/analysis-of-the-interactions-between-thioredoxin-and-20-selenoproteins-in-chicken
#8
Qi Liu, Jie Yang, Jingzeng Cai, Yilin Luan, Hamid Sattar, Man Liu, Shiwen Xu, Ziwei Zhang
Thioredoxin (Trx) is a small molecular protein with complicated functions in a number of processes, including inflammation, apoptosis, embryogenesis, cardiovascular disease, and redox regulation. Some selenoproteins, such as glutathione peroxidase (Gpx), iodothyronine deiodinase (Dio), and thioredoxin reductase (TR), are involved in redox regulation. However, whether there are interactions between Trx and selenoproteins is still not known. In the present paper, we used a Modeller, Hex 8.0.0, and the KFC2 Server to predict the interactions between Trx and selenoproteins...
March 2, 2017: Biological Trace Element Research
https://www.readbyqxmd.com/read/28222739/generation-of-donor-specific-tr1-cells-to-be-used-after-kidney-transplantation-and-definition-of-the-timing-of-their-in-vivo-infusion-in-the-presence-of-immunosuppression
#9
Bechara Mfarrej, Eleonora Tresoldi, Angela Stabilini, Alessia Paganelli, Rossana Caldara, Antonio Secchi, Manuela Battaglia
BACKGROUND: Operational tolerance is an alternative to lifelong immunosuppression after transplantation. One strategy to achieve tolerance is by T regulatory cells. Safety and feasibility of a T regulatory type 1 (Tr1)-cell-based therapy to prevent graft versus host disease in patients with hematological malignancies has been already proven. We are now planning to perform a Tr1-cell-based therapy after kidney transplantation. METHODS: Upon tailoring the lab-grade protocol to patients on dialysis, aims of the current work were to develop a clinical-grade compatible protocol to generate a donor-specific Tr1-cell-enriched medicinal product (named T10 cells) and to test the Tr1-cell sensitivity to standard immunosuppression in vivo to define the best timing of cell infusion...
February 21, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28166218/critical-role-of-irf1-and-batf-in-forming-chromatin-landscape-during-type-1-regulatory-cell-differentiation
#10
Katarzyna Karwacz, Emily R Miraldi, Maria Pokrovskii, Asaf Madi, Nir Yosef, Ivo Wortman, Xi Chen, Aaron Watters, Nicholas Carriero, Amit Awasthi, Aviv Regev, Richard Bonneau, Dan Littman, Vijay K Kuchroo
Type 1 regulatory T cells (Tr1 cells) are induced by interleukin-27 (IL-27) and have critical roles in the control of autoimmunity and resolution of inflammation. We found that the transcription factors IRF1 and BATF were induced early on after treatment with IL-27 and were required for the differentiation and function of Tr1 cells in vitro and in vivo. Epigenetic and transcriptional analyses revealed that both transcription factors influenced chromatin accessibility and expression of the genes required for Tr1 cell function...
April 2017: Nature Immunology
https://www.readbyqxmd.com/read/28158245/protein-kinase-c-theta-is-required-for-efficient-induction-of-il-10-secreting-t-cells
#11
Graham J Britton, Ruth E Mitchell, Bronwen R Burton, David C Wraith
Secretion of interleukin-10 (IL-10) by CD4+ T cells is an essential immunoregulatory mechanism. The work presented here assesses the role of the signaling molecule protein kinase C theta (PKCθ) in the induction of IL-10 expression in CD4+ T cells. Using wildtype and PKCθ-deficient Tg4 T cell receptor transgenic mice, we implemented a well-described protocol of repeated doses of myelin basic protein (MBP)Ac1-9[4Y] antigen to induce Tr1-like IL-10+ T cells. We find that PKCθ is required for the efficient induction of IL-10 following antigen administration...
2017: PloS One
https://www.readbyqxmd.com/read/28130449/interleukin-27-il-27-alleviates-bone-loss-in-estrogen-deficient-conditions-by-induction-of-early-growth-response-2-gene
#12
Priyanka Shukla, Mohd Nizam Mansoori, Manisha Kakaji, Manoj Shukla, Sushil Kumar Gupta, Divya Singh
A growing understanding of the bone remodeling process suggests that inflammation significantly contributes to the pathogenesis of osteoporosis. T cells and various cytokines contribute majorly to the estrogen deficiency-induced bone loss. Recent studies have identified the IL-12 cytokine family as consisting of pro-inflammatory IL-12 and IL-23 and the anti-inflammatory IL-27 and IL-35 cytokines. IL-27 exerts protective effects in autoimmune diseases like experimental autoimmune encephalomyelitis; however, its role in the pathogenesis of osteoporosis remains to be determined...
March 17, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28130148/broad-spectrum-antibiotic-enrofloxacin-modulates-contact-sensitivity-through-gut-microbiota-in-a-murine-model
#13
Anna Strzępa, Monika Majewska-Szczepanik, Francis M Lobo, Li Wen, Marian Szczepanik
BACKGROUND: Medical advances in the field of infection therapy has led to an increasing use of antibiotics, which, apart from eliminating pathogens, also partially eliminate naturally existing commensal bacteria. It has become increasingly clear that less exposure to microbiota early in life may contribute to the observed rise in "immune-mediated" diseases including autoimmunity and allergy. OBJECTIVE: We sought to test whether the change of gut microbiota with the broad spectrum antibiotic enrofloxacin will modulate contact sensitivity (CS) in mice...
January 24, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28094200/type-i-interferon-in-malaria-a-balancing-act
#14
Jason Paul Mooney, Samuel Crocodile Wassmer, Julius Clemence Hafalla
Type I interferons (IFN-Is) can now be considered as the wedge that balances clinical protection to malaria. New studies recently highlighted a central role for IFN-Is in orchestrating an immunoregulatory network leading to the dampening of proinflammatory responses, expansion of type 1 regulatory (Tr1) cells, and restriction of humoral immunity during malaria blood stage infection. Plasmacytoid dendritic cells (pDCs) were identified as the major source of IFN-Is. Here, we integrate the findings and provide a model for the mechanisms involved...
April 2017: Trends in Parasitology
https://www.readbyqxmd.com/read/28062696/prostaglandin-e2-inhibition-of-il-27-production-in-murine-dendritic-cells-a-novel-mechanism-that-involves-irf1
#15
Kirsten M Hooper, Jui-Hung Yen, Weimin Kong, Kate M Rahbari, Ping-Chang Kuo, Ana M Gamero, Doina Ganea
IL-27, a multifunctional cytokine produced by APCs, antagonizes inflammation by affecting conventional dendritic cells (cDC), inducing IL-10, and promoting development of regulatory Tr1 cells. Although the mechanisms involved in IL-27 induction are well studied, much less is known about the factors that negatively impact IL-27 expression. PGE2, a major immunomodulatory prostanoid, acts as a proinflammatory agent in several models of inflammatory/autoimmune disease, promoting primarily Th17 development and function...
February 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28003377/il-10-receptor-signaling-is-essential-for-tr1-cell-function-in-vivo
#16
Leonie Brockmann, Nicola Gagliani, Babett Steglich, Anastasios D Giannou, Jan Kempski, Penelope Pelczar, Maria Geffken, Bechara Mfarrej, Francis Huber, Johannes Herkel, Yisong Y Wan, Enric Esplugues, Manuela Battaglia, Christian F Krebs, Richard A Flavell, Samuel Huber
IL-10 is essential to maintain intestinal homeostasis. CD4(+) T regulatory type 1 (TR1) cells produce large amounts of this cytokine and are therefore currently being examined in clinical trials as T cell therapy in patients with inflammatory bowel disease. However, factors and molecular signals sustaining TR1 cell regulatory activity still need to be identified to optimize the efficiency and ensure the safety of these trials. We investigated the role of IL-10 signaling in mature TR1 cells in vivo. Double IL-10(eGFP) Foxp3(mRFP) reporter mice and transgenic mice with impairment in IL-10 receptor signaling were used to test the activity of TR1 cells in a murine inflammatory bowel disease model, a model that resembles the trials performed in humans...
February 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27977935/emergence-of-novel-pathogenic-streptomyces-species-by-site-specific-accretion-and-cis-mobilization-of-pathogenicity-islands
#17
Yucheng Zhang, Rosemary Loria
The main pathogenicity factor of Streptomyces species associated with the potato common scab disease is a nitrated diketopiperazine called thaxtomin A (ThxA). In Streptomyces scabiei (syn. S. scabies), which is thought to be the most ancient pathogenic Streptomyces species, the ThxA biosynthetic cluster is located within a mobile genomic island called the toxicogenic region (TR). Three attachment (att) sites further separate TR into two subregions (TR1 and TR2). TR1 contains the ThxA biosynthetic cluster and is conserved among several pathogenic Streptomyces species...
January 2017: Molecular Plant-microbe Interactions: MPMI
https://www.readbyqxmd.com/read/27974866/cd4-t-cell-fate-in-glomerulonephritis-a-tale-of-th1-th17-and-novel-treg-subtypes
#18
REVIEW
Christan F Krebs, Oliver M Steinmetz
Multiple studies have identified CD4(+) T cells as central players of glomerulonephritis (GN). Cells of the Th1 and Th17 responses cause renal tissue damage, while Tregs mediate protection. Recently, a high degree of plasticity among these T cell lineages was proposed. During inflammation, Th17 cells were shown to have the potential of transdifferentiation into Th1, Th2, or alternatively anti-inflammatory Tr1 cells. Currently available data from studies in GN, however, do not indicate relevant Th17 to Th1 or Th2 conversion, leaving the Th17 cell fate enigmatic...
2016: Mediators of Inflammation
https://www.readbyqxmd.com/read/27957666/decreased-expression-of-selenoproteins-as-a-poor-prognosticator-of-gastric-cancer-in-humans
#19
Xiuwen Lan, Jun Xing, Hongyu Gao, Sen Li, Lina Quan, Yang Jiang, Shaohua Ding, Yingwei Xue
The aim of the present study was to analyze the selenoprotein expression levels in gastric cancer patients. We enrolled 40 patients (29 males, 11 females) who were recently diagnosed with gastric cancer and 50 healthy people (30 males, 20 females) as controls. The expression of 25 selenoprotein genes (Dio1, Dio2, Dio3, Gpx1, Gpx2, Gpx3, Gpx4, Gpx6, SelH, SelI, SelK, SelM, SelN, SelO, SelP, SelS, SelT, SelV, SelW, SelX, Sel15, Sps2, TR1, TR2, and TR3) in human gastric cancer tissues, para-carcinoma tissues, adjacent normal gastric tissues, erythrocytes, and lymphocytes in the gastric cancer group and healthy control group was analyzed by qRT-PCR...
December 13, 2016: Biological Trace Element Research
https://www.readbyqxmd.com/read/27936058/modeling-the-role-of-lanthionine-synthetase-c-like-2-lancl2-in-the-modulation-of-immune-responses-to-helicobacter-pylori-infection
#20
Andrew Leber, Josep Bassaganya-Riera, Nuria Tubau-Juni, Victoria Zoccoli-Rodriguez, Monica Viladomiu, Vida Abedi, Pinyi Lu, Raquel Hontecillas
Immune responses to Helicobacter pylori are orchestrated through complex balances of host-bacterial interactions, including inflammatory and regulatory immune responses across scales that can lead to the development of the gastric disease or the promotion of beneficial systemic effects. While inflammation in response to the bacterium has been reasonably characterized, the regulatory pathways that contribute to preventing inflammatory events during H. pylori infection are incompletely understood. To aid in this effort, we have generated a computational model incorporating recent developments in the understanding of H...
2016: PloS One
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