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https://www.readbyqxmd.com/read/28749570/hepatocyte-derived-exosomes-promote-t-follicular-regulatory-cell-expansion-during-hcv-infection
#1
Dustin A Cobb, Lucy Golden-Mason, Hugo R Rosen, Young S Hahn
Hepatitis C virus (HCV) is a global health concern that can cause severe liver disease such as cirrhosis and hepatocellular carcinoma. Control of HCV requires vigorous T cell responses, yet CD4(+) T cells in chronic HCV patients are dysfunctional. T follicular regulatory (Tfr) cells are a subset of regulatory T cells that suppress T follicular helper (Tfh) cells and the generation of high affinity antibody-producing B cells. In this study, we examined the accumulation of Tfr cells in the liver compartment during chronic HCV infection and defined the cellular and molecular mechanisms underlying their expansion...
July 27, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28748534/mir-130b-directly-targets-arhgap1-to-drive-activation-of-a-metastatic-cdc42-pak1-ap1-positive-feedback-loop-in-ewing-sarcoma
#2
Laura Satterfield, Ryan Shuck, Lyazat Kurenbekova, Wendy Allen-Rhoades, Dean Edwards, Shixia Huang, Kimal Rajapakshe, Cristian Coarfa, Lawrence A Donehower, Jason T Yustein
Ewing Sarcoma (ES) is a highly aggressive bone tumor with peak incidence in the adolescent population. It has a high propensity to metastasize, which is associated with dismal survival rates of approximately 25%. To further understand mechanisms of metastasis we investigated microRNA regulatory networks in ES. Our studies focused on miR-130b due to our analysis that enhanced expression of this microRNA has clinical relevance in multiple sarcomas, including ES. Our studies provide insights into a novel positive feedback network involving the direct regulation of miR-130b and activation of downstream signaling events contributing towards sarcoma metastasis...
July 27, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28747348/lactation-based-maternal-educational-immunity-crosses-mhc-class-i-barriers-and-can-impart-th1-immunity-to-th2-biased-recipients
#3
Mrinal K Ghosh, H Konrad Muller, Ameae M Walker
We have previously demonstrated lactational transfer of T cell-based immunity from dam to foster pup. In the short term, a significant part of transferred immunity is passive cellular immunity. However, as time progresses, this is replaced by what we have described as maternal educational immunity such that by young adulthood, all immune cells responding to a foster dam immunogen are the product of the foster pup's thymus. To reduce confounding factors, this original demonstration used congenic/syngeneic dam and foster pup pairs...
July 26, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28746783/cd73-expression-identifies-a-subset-of-igm-antigen-experienced-cells-with-memory-attributes-that-is-t-cell-and-cd40-signaling-dependent
#4
Lucas D'Souza, Sneh Lata Gupta, Vineeta Bal, Satyajit Rath, Anna George
B cell memory was long characterized as isotype-switched, somatically mutated and germinal center (GC)-derived. However, it is now clear that the memory pool is a complex mixture that includes unswitched and unmutated cells. Further, expression of CD73, CD80 and CD273 has allowed the categorization of B cell memory into multiple subsets, with combinatorial expression of the markers increasing with GC progression, isotype-switching and acquisition of somatic mutations. We have extended these findings to determine whether these markers can be used to identify IgM memory phenotypically as arising from T-dependent versus T-independent responses...
July 26, 2017: Immunology
https://www.readbyqxmd.com/read/28746369/single-and-combined-effect-of-retinoic-acid-and-rapamycin-modulate-the-generation-activity-and-homing-potential-of-induced-human-regulatory-t-cells
#5
Enzo Candia, Paz Reyes, Camila Covian, Francisco Rodriguez, Nicolas Wainstein, Jorge Morales, Claudio Mosso, Mario Rosemblatt, Juan Alberto Fierro
Adoptive transfer of CD4+CD25+FOXP3+ regulatory T cells (Treg cells) has been successfully utilized to treat graft versus host disease and represents a promising strategy for the treatment of autoimmune diseases and transplant rejection. The aim of this study was to evaluate the effects of all-trans retinoic acid (atRA) and rapamycin (RAPA) on the number, phenotype, homing markers expression, DNA methylation, and function of induced human Treg cells in short-term cultures. Naive T cells were polyclonally stimulated and cultured for five days in the presence of different combinations of IL-2, TGF-β1, atRA and RAPA...
2017: PloS One
https://www.readbyqxmd.com/read/28742217/the-inflammatory-cytokine-interferon-gamma-inhibits-sortilin-1-expression-in-hepatocytes-via-the-jak-stat-pathway
#6
John Pirault, Konstantinos A Polyzos, Marcelo H Petri, Daniel Fj Ketelhuth, Magnus Bäck, Göran K Hansson
Sortilin-1, a receptor of the VPS10p family, has been associated with cardiovascular disease in genome-wide association studies. It is implicated in lipoprotein metabolism, secretion of proprotein convertase subtilisin/kexin type 9 (PCSK9) and secretion of inflammatory cytokines. However, its own regulation remains unclear. Chronic inflammation is a hallmark of atherosclerosis and absence of regulatory T (Treg) cells is associated with reduced protein expression of sortilin-1 in the liver. Therefore, we postulated that mediator(s) of inflammation known to be downregulated by regulatory T cells may modulate sortilin-1 expression...
July 25, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28741728/ebi2-contributes-to-the-induction-of-thymic-central-tolerance-in-mice-by-promoting-rapid-motility-of-medullary-thymocytes
#7
Sanghee Ki, Hiran M Thyagarajan, Zicheng Hu, Jessica N Lancaster, Lauren I R Ehrlich
Maturing thymocytes enter the thymic medulla, where they encounter numerous self-antigens presented by antigen presenting cells (APCs). Those thymocytes that are strongly self-reactive undergo either negative selection or diversion into the regulatory T cell lineage. Although the majority of the proteome is expressed in the medulla, many self-antigens are expressed by only a minor fraction of medullary APCs; thus, thymocytes must efficiently enter the medulla and scan APCs to ensure central tolerance. Chemokine receptors promote lymphocyte migration, organization within tissues, and interactions with APCs in lymphoid organs...
July 25, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28741409/foxp3-expression-in-lymph-node-metastases-in-patients-with-head-and-neck-cancer
#8
Mehtap Boduc, Marion Roessler, Robert Mandic, Christoph Netzer, Christian Güldner, Ute Walliczek-Dworschak, Boris A Stuck, Magis Mandapathil
INTRODUCTION: The prevalence and activity of regulatory T cells in patients with cancer correlates with poor prognosis. These cells are characterized by their expression of Forkhead box protein-3 (Foxp3). Squamous cell carcinoma is the most prevalent type of cancer in the head and neck region with overall poor survival rates, also due to early spread of metastatic cells. MATERIAL AND METHODS: Primary tumor specimens as well as lymph node specimens harvested during neck dissection of 65 patients with a diagnosis of HNSCC were subjected to immunohistochemical and H-score analysis of Foxp3 expression...
July 25, 2017: Acta Oto-laryngologica
https://www.readbyqxmd.com/read/28740491/nod-like-receptor-p3-inflammasome-controls-protective-th1-th17-immunity-against-pulmonary-paracoccidioidomycosis
#9
Claudia Feriotti, Eliseu Frank de Araújo, Flavio Vieira Loures, Tania Alves da Costa, Nayane Alves de Lima Galdino, Dario Simões Zamboni, Vera Lucia Garcia Calich
The NOD-like receptor P3 (NLRP3) inflammasome is an intracellular multimeric complex that triggers the activation of inflammatory caspases and the maturation of IL-1β and IL-18, important cytokines for the innate immune response against pathogens. The functional NLRP3 inflammasome complex consists of NLRP3, the adaptor protein apoptosis-associated speck-like protein, and caspase-1. Various molecular mechanisms were associated with NLRP3 activation including the presence of extracellular ATP, recognized by the cell surface P2X7 receptor (P2X7R)...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28736999/regulatory-t-cell-subsets-in-peripheral-blood-of-celiac-disease-patients-and-tlr2-expression-correlation-with-oxidative-stress
#10
Sanjay Kumar, Sadhna Lal, Archana Bhatnagar
The study was carried out to study expression of Toll like receptors 2 (TLR2), natural/inducible Treg and Interferon-γ alongside oxidative stress and understand their significance in pediatric samples. Influence of oxidative stress on Celiac Disease was analysed by evaluating lipid peroxidation, reduced glutathione, Glutathione peroxidase, etc. A comparison was performed among CD patients, CD patients on gluten free diet (GFD), and healthy controls. Peripheral nTregs exhibited a similar pattern of reduced numbers in CD and GFD cases when compared to healthy controls...
July 24, 2017: APMIS: Acta Pathologica, Microbiologica, et Immunologica Scandinavica
https://www.readbyqxmd.com/read/28736941/in-vivo-neutralization-of-%C3%AE-4-and-%C3%AE-7-integrins-inhibits-eosinophil-trafficking-and-prevents-lung-injury-during-tropical-pulmonary-eosinophilia-in-mice
#11
Pankaj Sharma, Aditi Sharma, Mrigank Srivastava
Integrins regulate leukocyte trafficking during homeostasis and inflammatory conditions. However, the role of α4 and β7 integrins in guiding eosinophil transmigration into the lungs during filarial manifestation of Tropical Pulmonary Eosinophilia (TPE) has not been explored. In this study, mice exhibiting TPE manifestations were administered with in vivo neutralizing antibodies against integrins α4 and β7 or their combination and immuno-pathological parameters were evaluated. Results show an intact lung barrier, significantly lower lung inflammation and reduced eosinophil counts in the Bronchoalveolar lavage fluid and lungs of mice receiving anti-α4(+) β7 treatment...
July 24, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28736829/clonal-analysis-of-regulatory-t-cell-defect-in-patients-with-autoimmune-polyendocrine-syndrome-type-1-suggests-intrathymic-impairment
#12
Tuisku-Tuulia Koivula, Sini M Laakso, Heikki J Niemi, Eliisa Kekäläinen, Pia Laine, Lars Paulin, Petri Auvinen, T Petteri Arstila
Mutations in the Autoimmune Regulator (AIRE) gene disrupt thymic T cell development and negative selection, leading to the recessively inherited polyendocrine autoimmune disease APS-1 (autoimmune polyendocrine syndrome type 1). The patients also have a functional defect in the FOXP3(+) regulatory T cell population, but its origin is unclear. Here we have used T cell receptor sequencing to analyze the clonal relationship of major CD4(+) T cell subsets in 3 patients and 3 healthy controls. The naive regulatory T cells showed little overlap with helper T cell subsets, supporting divergence in the thymus...
July 22, 2017: Scandinavian Journal of Immunology
https://www.readbyqxmd.com/read/28735899/mot1-ino80c-and-nc2-function-coordinately-to-regulate-pervasive-transcription-in-yeast-and-mammals
#13
Yong Xue, Suman K Pradhan, Fei Sun, Constantinos Chronis, Nancy Tran, Trent Su, Christopher Van, Ajay Vashisht, James Wohlschlegel, Craig L Peterson, H T Marc Timmers, Siavash K Kurdistani, Michael F Carey
Pervasive transcription initiates from cryptic promoters and is observed in eukaryotes ranging from yeast to mammals. The Set2-Rpd3 regulatory system prevents cryptic promoter function within expressed genes. However, conserved systems that control pervasive transcription within intergenic regions have not been well established. Here we show that Mot1, Ino80 chromatin remodeling complex (Ino80C), and NC2 co-localize on chromatin and coordinately suppress pervasive transcription in S. cerevisiae and murine embryonic stem cells (mESCs)...
July 15, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28731485/th17-regulatory-t-cell-imbalance-in-sepsis-patients-with-multiple-organ-dysfunction-syndrome-attenuated-by-high-volume-hemofiltration
#14
Jiguang Guo, Wu Tao, Dan Tang, Jianbin Zhang
BACKGROUND: We assessed the Th17 (T-helper cell)/Treg (Regulatory T cell) imbalance in sepsis patients with multiple organ dysfunction syndrome (MODS) and the clinical benefits of continuous high-volume hemofiltration (HVHF). METHODS: 48 sepsis patients, including 22 patients with MODS (MODS group, n = 22) and 26 without (non-MODS group, n = 26), and 20 healthy volunteer controls were enrolled. The patients in MODS group were randomly divided into the continuous blood purification (CBP) group (n = 11) receiving conventional comprehensive treatment plus high-volume hemofiltration and the non-CBP group (n = 11) receiving conventional comprehensive treatment only...
July 14, 2017: International Journal of Artificial Organs
https://www.readbyqxmd.com/read/28731226/curcumin-converts-foxp3-regulatory-t-cells-to-t-helper-1-cells-in-patients-with-lung-cancer
#15
JianYong Zou, ChunHua Su, HongHe Luo, YiYan Lei, Bo Zeng, HaoShuai Zhu, ZhenGuang Chen
The regulatory T cells (Treg) play an important role in the tumor tolerance. The methods to regulate the Treg population in cancer-bearing hosts are limited currently. The effect of curcumin on inhibiting cancer has been recognized, but the mechanism remains elusive. This study tests a hypothesis that administration of curcumin down regulates Tregs in lung cancer (LC) patients. In this study, a group of LC patients was treated with curcumin. The peripheral Tregs and T helper (Th) 1 cells were analyzed by flow cytometry...
July 21, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28724766/a-unique-t-cell-receptor-amino-acid-sequence-selected-by-htlv-i-tax301-309-specific-cytotoxic-t-cells-in-hla-a24-02-asymptomatic-carriers-and-adult-t-cell-leukemia-lymphoma-patients
#16
Yuko Ishihara, Yukie Tanaka, Seiichiro Kobayashi, Koji Kawamura, Hideki Nakasone, Ayumi Gomyo, Jin Hayakawa, Masaharu Tamaki, Yu Akahoshi, Naonori Harada, Machiko Kusuda, Kazuaki Kameda, Tomotaka Ugai, Hidenori Wada, Kana Sakamoto, Miki Sato, Kiriko Terasako-Saito, Misato Kikuchi, Shun-Ichi Kimura, Aki Tanihara, Shinichi Kako, Kaoru Uchimaru, Yoshinobu Kanda
We previously reported that the T-cell receptor (TCR) repertoire of HTLV-I Tax301-309-specific CD8(+) cytotoxic T-cells (Tax-CTLs) was highly restricted and a particular amino acid sequence motif, "PDR", was conserved among HLA-A*24:02(+) ATL patients who have undergone allogeneic hematopoietic cell transplantation (allo-HSCT). Furthermore, we found that donor-derived PDR+CTLs selectively expanded in ATL long-term HSCT survivors with strong CTL activity against HTLV-I. On the other hand, the TCR repertoires in Tax-CTL of asymptomatic HTLV-I carriers (ACs) remain unclear...
July 19, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28724573/a-single-dose-of-peripherally-infused-egfrviii-directed-car-t-cells-mediates-antigen-loss-and-induces-adaptive-resistance-in-patients-with-recurrent-glioblastoma
#17
Donald M O'Rourke, MacLean P Nasrallah, Arati Desai, Jan J Melenhorst, Keith Mansfield, Jennifer J D Morrissette, Maria Martinez-Lage, Steven Brem, Eileen Maloney, Angela Shen, Randi Isaacs, Suyash Mohan, Gabriela Plesa, Simon F Lacey, Jean-Marc Navenot, Zhaohui Zheng, Bruce L Levine, Hideho Okada, Carl H June, Jennifer L Brogdon, Marcela V Maus
We conducted a first-in-human study of intravenous delivery of a single dose of autologous T cells redirected to the epidermal growth factor receptor variant III (EGFRvIII) mutation by a chimeric antigen receptor (CAR). We report our findings on the first 10 recurrent glioblastoma (GBM) patients treated. We found that manufacturing and infusion of CAR-modified T cell (CART)-EGFRvIII cells are feasible and safe, without evidence of off-tumor toxicity or cytokine release syndrome. One patient has had residual stable disease for over 18 months of follow-up...
July 19, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28722110/renal-infiltrating-cd11c-cells-are-pathogenic-in-murine-lupus-nephritis-through-promoting-cd4-t-cell-responses
#18
Xiaofeng Liao, Jingjing Ren, Alec Reihl, Tharshikha Pirapakaran, Bharath Sreekumar, Thomas E Cecere, Christopher M Reilly, Xin M Luo
Lupus nephritis (LN) is a major manifestation of systemic lupus erythematosus (SLE) causing morbidity and mortality in 40-60% of SLE patients. The pathogenic mechanisms of LN are not completely understood. Recent studies have demonstrated the presence of various immune cell populations in lupus nephritic kidneys of both SLE patients and lupus-prone mice. These cells may play important pathogenic or regulatory roles in situ to promote or sustain LN. Here, using lupus-prone mouse models, we showed the pathogenic role of a kidney-infiltrating CD11c(+) myeloid cell population in LN...
July 19, 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/28719513/dihydrofolate-reductase-genetic-polymorphisms-affect-methotrexate-dose-requirements-in-pediatric-patients-with-acute-lymphoblastic-leukemia-on-maintenance-therapy
#19
Guillermo Gervasini, Silvia G de Murillo, Mercedes Jiménez, María D de la Maya, Jose M Vagace
We have aimed to determine the effect of polymorphisms in regulatory regions of the DHFR gene in relation to methotrexate (MTX) dose adjustments and drug-induced toxicity in children on maintenance therapy for acute lymphoblastic leukemia (ALL). In total, 41 children diagnosed with ALL were screened for 3 tag-single nucleotide polymorphisms in the DHFR promoter (C-1610G, C-680G/T, A-317G) and an intronic 19-bp insertion/deletion. Genotypes were analyzed in relation to dose requirements and toxicity. The percentage of MTX dose administered (with respect to protocol-recommended values) was affected by DHFR polymorphisms...
July 17, 2017: Journal of Pediatric Hematology/oncology
https://www.readbyqxmd.com/read/28719035/melatonin-inhibits-nucleus-pulposus-np-cell-proliferation-and-extracellular-matrix-ecm-remodeling-via-the-melatonin-membrane-receptors-mediated-pi3k-akt-pathway
#20
Zheng Li, Xingye Li, Chong Chen, Matthew T V Chan, William Ka Kei Wu, Jianxiong Shen
Pinealectomy in vertebrates accelerated intervertebral disc degeneration (IDD). However, the potential mechanisms, particularly, melatonin's role is still to be clarified. In this study, for first time, melatonin membrane receptors of MT1 and MT2 were found to be present in the human intervertebral disc tissues and nucleus pulposus (NP) cells, respectively. Melatonin treatment significantly inhibited NP cell proliferation in dose- dependent manner. Accordingly, melatonin down-regulated gene expression of cyclin D1, PCNA, matrix metallopeptidases-3 and -9 and upregulated gene expression of collagen type II alpha 1 chain and aggrecan in NP cells...
July 18, 2017: Journal of Pineal Research
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