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https://www.readbyqxmd.com/read/28689297/estrogen-protects-both-sexes-against-eae-by-promoting-common-regulatory-cell-subtypes-independent-of-endogenous-estrogen
#1
Hilary A Seifert, Gil Benedek, Ha Nguyen, Gail Kent, Arthur A Vandenbark, Halina Offner
Autoimmune diseases including multiple sclerosis predominantly affect females. Although high levels of sex hormones, particularly estrogen (E2), can reduce proinflammatory immune responses, it remains unclear if a lack of endogenous sex hormones might affect treatment with exogenous sex hormones. Pretreatment with E2 almost completely prevents intact female and male mice from developing clinical and histological signs of experimental autoimmune encephalomyelitis (EAE) by promoting various regulatory immune cell phenotypes...
July 8, 2017: Metabolic Brain Disease
https://www.readbyqxmd.com/read/28674210/chinese-medicine-ginseng-and-astragalus-granules-ameliorate-autoimmune-diabetes-by-upregulating-both-cd4-foxp3-and-cd8-cd122-pd1-regulatory-t-cells
#2
Yeshu Wang, Qingfeng Xie, Chun-Ling Liang, Qiaohuang Zeng, Zhenhua Dai
Type 1 diabetes mellitus (T1DM) is an autoimmune disease mainly mediated by effector T cells that are activated by autoantigen, thereby resulting in the destruction of pancreatic islets and deficiency of insulin. Cyclosporine is widely used as an immunosuppressant that suppresses autoimmunity in clinic. However, continuous treatments with conventional immunosuppressive drugs may cause severe side effects. Therefore it is important to seek alternative medicine. Chinese medicine Ginseng and Astragalus granule (GAG) was used to successfully treat type 2 diabetes mellitus in clinic in China...
June 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28652399/c-rel-and-i%C3%AE%C2%BAbns-govern-common-and-independent-steps-of-regulatory-t-cell-development-from-novel-cd122-expressing-pre-precursors
#3
Marc Schuster, Carlos Plaza-Sirvent, Anne-Marie Matthies, Ulrike Heise, Andreas Jeron, Dunja Bruder, Alexander Visekruna, Jochen Huehn, Ingo Schmitz
Foxp3-expressing regulatory T cells (Tregs) are essential regulators of immune homeostasis and, thus, are prime targets for therapeutic interventions of diseases such as cancer and autoimmunity. c-REL and IκBNS are important regulators of Foxp3 induction in Treg precursors upon γ-chain cytokine stimulation. In c-REL/IκBNS double-deficient mice, Treg numbers were dramatically reduced, indicating that together, c-REL and IκBNS are pivotal for Treg development. However, despite the highly reduced Treg compartment, double-deficient mice did not develop autoimmunity even when aged to more than 1 y, suggesting that c-REL and IκBNS are required for T cell effector function as well...
June 26, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28652304/thymic-progenitors-of-tcr%C3%AE-%C3%AE-cd8%C3%AE-%C3%AE-intestinal-intraepithelial-lymphocytes-require-rasgrp1-for-development
#4
Dominic P Golec, Romy E Hoeppli, Laura M Henao Caviedes, Jillian McCann, Megan K Levings, Troy A Baldwin
Strong T cell receptor (TCR) signaling largely induces cell death during thymocyte development, whereas weak TCR signals induce positive selection. However, some T cell lineages require strong TCR signals for differentiation through a process termed agonist selection. The signaling relationships that underlie these three fates are unknown. RasGRP1 is a Ras activator required to transmit weak TCR signals leading to positive selection. Here, we report that, despite being dispensable for thymocyte clonal deletion, RasGRP1 is critical for agonist selection of TCRαβ(+)CD8αα intraepithelial lymphocyte (IEL) progenitors (IELps), even though both outcomes require strong TCR signaling...
June 26, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28555090/the-distribution-of-activation-markers-and-selectins-on-peripheral-t-lymphocytes-in-preeclampsia
#5
Anna Bajnok, Maria Ivanova, János Rigó, Gergely Toldi
INTRODUCTION: Impaired maternal immune tolerance resulting in systemic inflammation plays a pivotal role in the pathogenesis of preeclampsia. Phenotypical changes of monocytes and neutrophil granulocytes have already been studied in preeclampsia, and some studies also included T lymphocyte activation markers; however, the results are controversial and a comprehensive analysis of activation markers is lacking. The characteristics of cellular adhesion molecules in preeclampsia are yet to be described...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28507024/cutting-edge-differential-fine-tuning-of-il-2-and-il-15-dependent-functions-by-targeting-their-common-il-2-15r%C3%AE-%C3%AE-c-receptor
#6
Dihia Meghnem, Sébastien Morisseau, Marie Frutoso, Kilian Trillet, Mike Maillasson, Isabelle Barbieux, Sarah Khaddage, Isabelle Leray, Markus Hildinger, Agnès Quéméner, Yannick Jacques, Erwan Mortier
Interleukin 2 and IL-15 are two closely related cytokines, displaying important functions in the immune system. They share the heterodimeric CD122/CD132 receptor to deliver their signals within target cells. Their specificity of action is conferred by their α receptor chains, IL-2Rα and IL-15Rα. By combining an increased affinity for CD122 and an impaired recruitment of CD132, we have generated an original molecule named IL-2Rβ/γ (CD122/CD132) inhibitor (BiG), targeting the CD122/CD132 receptor. BiG efficiently inhibited IL-15- and IL-2-dependent functions of primary cells, including CD8 T and NK cells, in vitro and in vivo...
June 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28445940/suppression-of-allograft-rejection-by-cd8-cd122-pd-1-tregs-is-dictated-by-their-fas-ligand-initiated-killing-of-effector-t-cells-versus-fas-mediated-own-apoptosis
#7
Huazhen Liu, Yeshu Wang, Qiaohuang Zeng, Yu-Qun Zeng, Chun-Ling Liang, Feifei Qiu, Hong Nie, Zhenhua Dai
Mounting evidence has shown that naturally occurring CD8+CD122+ T cells are regulatory T cells (Tregs) that suppress both autoimmunity and alloimmunity. We have previously shown that CD8+CD122+PD-1+ Tregs not only suppress allograft rejection, but also are more potent in suppression than conventional CD4+CD25+ Tregs. However, the mechanisms underlying their suppression of alloimmunity are not well understood. In an adoptive T-cell transfer model of mice lacking lymphocytes, we found that suppression of skin allograft rejection by CD8+CD122+PD-1+ Tregs was mostly dependent on their expression of Fas ligand as either lacking Fas ligand or blocking it with antibodies largely abolished their suppression of allograft rejection mediated by transferred T cells...
April 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28208073/temporal-regulation-of-wnt-%C3%AE-catenin-signaling-is-important-for-invariant-nkt-cell-development-and-terminal-maturation
#8
Kalyani Pyaram, Jyoti Misra Sen, Cheong-Hee Chang
The Wnt/β-catenin signaling pathway plays important roles during various cellular functions including survival and proliferation of immune cells. The critical role of this pathway in conventional T cell development is established but little is known about its contributions to innate T cell development. In this study, we found that β-catenin level, an indication of the strength of Wnt/β-catenin signaling, is regulated during invariant NKT (iNKT) cell development. β-catenin levels were greatly increased during iNKT cell selection from double positive thymocytes to Stage 0 of iNKT cell development and during subsequent development to Stage 1...
May 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28164571/establishment-of-a-novel-myelodysplastic-syndrome-mds-xenotransplantation-model
#9
Ling Ma, Xia Zhang, Zhiqiong Wang, Yan Chen, Jia Wei, Lihua Hu
BACKGROUND: Myelodysplastic syndrome (MDS) is a clonal disease of the elderly characterized by chronic cytopenia, dysplasia, and a high risk of progression to acute myeloid leukemia (AML). Up until now, few animal models that fully recapitulate clinical features of this disease have been available. METHODS: This study aimed to establish a new MDS xenograft model utilizing a human MDS-derived cell line with heterozygous Y641C mutation of EZH2 (SKM-1). 1 x 107 SKM-1 cells were inoculated into anti-mouse CD122 monoantibody conditioned nonobese diabetic severe combined immunodeficiency (NOD/SCID) mice by intravenous injection...
September 1, 2016: Clinical Laboratory
https://www.readbyqxmd.com/read/28104168/meld-and-child-pugh-scores-are-related-to-immune-status-of-intrahepatic-natural-killer-cells-in-liver-transplant-candidates
#10
N Tanimine, Y Tanaka, T Abe, J Piao, K Ishiyama, T Kobayashi, K Ide, M Ohira, H Tahara, S Shimizu, Y Saeki, H Sakai, T Yano, H Ohdan
BACKGROUND: The role and phenotypic alterations of intrahepatic natural killer (NK) cells in liver disease were investigated. Although intrahepatic NK cells reportedly functionally deteriorate in the fibrotic liver, it remains unclear how the clinical severity of liver disease affects intrahepatic NK cells in patients with advanced liver failure. METHODS: We analyzed the phenotypic properties of intrahepatic NK cells by using mononuclear cells extracted from ex vivo liver perfusate effluents from patients who underwent liver transplantation...
January 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/28098193/non-pathogenic-tissue-resident-cd8-t-cells-uniquely-accumulate-in-the-brains-of-lupus-prone-mice
#11
Peter A Morawski, Chen-Feng Qi, Silvia Bolland
Severe lupus often includes psychiatric and neurological sequelae, although the cellular contributors to CNS disease remain poorly defined. Using intravascular staining to discriminate tissue-localized from blood-borne cells, we find substantial accumulation of CD8(+) T cells relative to other lymphocytes in brain tissue, which correlates with lupus disease and limited neuropathology. This is in contrast to all other affected organs, where infiltrating CD4(+) cells are predominant. Brain-infiltrating CD8(+) T cells represent an activated subset of those found in the periphery, having a resident-memory phenotype (CD69(+)CD122(-)PD1(+)CD44(+)CD62L(-)) and expressing adhesion molecules (VLA-4(+)LFA-1(+)) complementary to activated brain endothelium...
January 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/27982126/interleukin-12-bypasses-common-gamma-chain-signalling-in-emergency-natural-killer-cell-lymphopoiesis
#12
Isabel Ohs, Maries van den Broek, Kathrin Nussbaum, Christian Münz, Sebastian J Arnold, Sergio A Quezada, Sonia Tugues, Burkhard Becher
Differentiation and homeostasis of natural killer (NK) cells relies on common gamma-chain (γc)-dependent cytokines, in particular IL-15. Consequently, NK cells do not develop in mice with targeted γc deletion. Herein we identify an alternative pathway of NK-cell development driven by the proinflammatory cytokine IL-12, which can occur independently of γc-signalling. In response to viral infection or upon exogenous administration, IL-12 is sufficient to elicit the emergence of a population of CD122(+)CD49b(+) cells by targeting NK-cell precursors (NKPs) in the bone marrow (BM)...
December 16, 2016: Nature Communications
https://www.readbyqxmd.com/read/27766099/nfat2-regulates-generation-of-innate-like-cd8-t-lymphocytes-and-cd8-t-lymphocytes-responses
#13
Emilia Pachulec, Vanessa Neitzke-Montinelli, João P B Viola
Nuclear factor of activated T cells (NFAT) 2 null mutant mice die in utero of cardiac failure, precluding analysis of the role of NFAT2 in lymphocyte responses. Only the NFAT2(-/-)/Rag-1(-/-) chimeric mice model gave insight into the role of NFAT2 transcription factor in T lymphocyte development, activation, and differentiation. As reports are mainly focused on the role of NFAT2 in CD4(+) T lymphocytes activation and differentiation, we decided to investigate NFAT2's impact on CD8(+) T lymphocyte responses...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27727279/regulatory-t-cell-responses-in-participants-with-type-1-diabetes-after-a-single-dose-of-interleukin-2-a-non-randomised-open-label-adaptive-dose-finding-trial
#14
RANDOMIZED CONTROLLED TRIAL
John A Todd, Marina Evangelou, Antony J Cutler, Marcin L Pekalski, Neil M Walker, Helen E Stevens, Linsey Porter, Deborah J Smyth, Daniel B Rainbow, Ricardo C Ferreira, Laura Esposito, Kara M D Hunter, Kevin Loudon, Kathryn Irons, Jennie H Yang, Charles J M Bell, Helen Schuilenburg, James Heywood, Ben Challis, Sankalpa Neupane, Pamela Clarke, Gillian Coleman, Sarah Dawson, Donna Goymer, Katerina Anselmiova, Jane Kennet, Judy Brown, Sarah L Caddy, Jia Lu, Jane Greatorex, Ian Goodfellow, Chris Wallace, Tim I Tree, Mark Evans, Adrian P Mander, Simon Bond, Linda S Wicker, Frank Waldron-Lynch
BACKGROUND: Interleukin-2 (IL-2) has an essential role in the expansion and function of CD4+ regulatory T cells (Tregs). Tregs reduce tissue damage by limiting the immune response following infection and regulate autoreactive CD4+ effector T cells (Teffs) to prevent autoimmune diseases, such as type 1 diabetes (T1D). Genetic susceptibility to T1D causes alterations in the IL-2 pathway, a finding that supports Tregs as a cellular therapeutic target. Aldesleukin (Proleukin; recombinant human IL-2), which is administered at high doses to activate the immune system in cancer immunotherapy, is now being repositioned to treat inflammatory and autoimmune disorders at lower doses by targeting Tregs...
October 2016: PLoS Medicine
https://www.readbyqxmd.com/read/27683954/novel-model-of-double-transgenic-mouse-results-in-autoimmune-diabetes-in-males
#15
Sylvie Chabot, Fernando Alvarez, Abdelaziz Amrani, Idriss Djilali-Saiah
Identifying the type of diabetogenic CD8(+) T cells that initiate autoimmune diabetes (AID) is a critical step in designing appropriate strategies for the early detection of beta cell-directed autoimmunity and its progression to diabetes. We generated a novel double transgenic (Tg) mouse model on the naturally diabetes resistant C57Bl/6 background, co-expressing two transgenes including a specific TCR anti-lymphocytic choriomeningitis virus nucleoprotein (LCMV-NP) carried by CD8(+) T cells and LCMV-NP (as neo-self antigen) expressed by pancreatic beta cells...
August 11, 2016: Autoimmunity
https://www.readbyqxmd.com/read/27651429/placenta-derived-decidual-stromal-cells-alter-il-2r-expression-and-signaling-in-alloantigen-activated-t-cells
#16
Tom Erkers, Martin Solders, Lotte Verleng, Cecilia Bergström, Arwen Stikvoort, Lalit Rane, Silvia Nava, Olle Ringdén, Helen Kaipe
This study investigated how stromal cells affect the IL-2 pathway in alloantigen-activated T cells. We found that decidual stromal cells (DSCs) from term placentas promoted a high production of IL-2 in cultures with alloantigen-activated T cells. The intensity of expression of cluster of differentiation 25 (CD25; IL-2Rα) on T cells was increased by DSCs, whereas the frequency and intensity of expression of the signaling subunits CD122 (IL-2Rβ) and CD132 (IL-2Rγc) were reduced. Consequently, uptake of IL-2 and STAT5 phosphorylation (pSTAT5) was abrogated...
September 20, 2016: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/27608299/the-tyrosine-kinase-inhibitor-tyrphostin-ag126-reduces-activation-of-inflammatory-cells-and-increases-foxp3-regulatory-t-cells-during-pathogenesis-of-rheumatoid-arthritis
#17
Sheikh Fayaz Ahmad, Mushtaq Ahmad Ansari, Ahmed Nadeem, Khairy M A Zoheir, Saleh A Bakheet, Othman A Al-Shabanah, Ammar Cherkess Al Rikabi, Sabry M Attia
Protein tyrosine kinases are key mediators of the signal transduction cascades that control expression of many genes involved in the induction of inflammation caused by arthritis. Here we investigate the effect of the tyrosine kinase inhibitor tyrphostin AG126 on a mouse model of adjuvant-induced arthritis (AIA). We report that when given at 5mg/kg i.p. every 48h from days 0-21, AG126 exerts potent anti-arthritic effects. Further, we investigated the role of AG126 on the key mediators of arthritic inflammation, namely, edema, arthritic score, presence of immunophenotypes including Foxp3(+), CD4(+)Foxp3(+), and CD25(+)Foxp3(+) T regulatory (Treg) cells, as well as pro- and anti-inflammatory mediators...
October 2016: Molecular Immunology
https://www.readbyqxmd.com/read/27601261/nk-cell-development-requires-tsc1-dependent-negative-regulation-of-il-15-triggered-mtorc1-activation
#18
Meixiang Yang, Shasha Chen, Juan Du, Junming He, Yuande Wang, Zehua Li, Guangao Liu, Wanwen Peng, Xiaokang Zeng, Dan Li, Panglian Xu, Wei Guo, Zai Chang, Song Wang, Zhigang Tian, Zhongjun Dong
Activation of metabolic signalling by IL-15 is required for natural killer (NK) cell development. Here we show that Tsc1, a repressor of mTOR, is dispensable for the terminal maturation, survival and function of NK cells but is critical to restrict exhaustive proliferation of immature NK cells and activation downstream of IL-15 during NK cell development. Tsc1 is expressed in immature NK cells and is upregulated by IL-15. Haematopoietic-specific deletion of Tsc1 causes a marked decrease in the number of NK cells and compromises rejection of 'missing-self' haematopoietic tumours and allogeneic bone marrow...
2016: Nature Communications
https://www.readbyqxmd.com/read/27426071/-advances-in-the-research-of-biological-characters-and-pathophysiological-effects-of-dendritic-epidermal-t-lymphocytes
#19
Y S Li, W F He, J Wu
The maturation of dendritic epidermal T lymphocytes (DETCs) in thymus needs ligand-mediated positive selection, and positive selection together with V3γ(+) γδT lymphocytes intrinsic program features order DETCs to specifically migrate to epidermis. Positive selection promotes DETCs to express CD122, which is vital for DETCs to survive and proliferate in skin. DETCs possess memory-like phenotype and are able to rapidly respond to danger signals when they move out from thymus. NKG2D, junctional adhesion molecule-like protein and 2B4 are demonstrated to participate in DETCs activation, except for ligands of T lymphocytes receptor...
January 2016: Zhonghua Shao Shang za Zhi, Zhonghua Shaoshang Zazhi, Chinese Journal of Burns
https://www.readbyqxmd.com/read/27228385/a-simple-rapid-and-highly-sensitive-electrochemical-dna-sensor-for-the-detection-of-%C3%AE-and-%C3%AE-thalassemia-in-china
#20
Pei-Qi Chen, Qian-Ni Liang, Tao-Sheng Huang, Tian-Cai Liu, Ming Li
BACKGROUND: Because of the life-consuming treatment and severe consequences associated with thalassemia, it is more effective to prevent than cure thalassemia. Rapid and sensitive detection is critical for controlling thalassemia. In this study, we developed a rapid and accurate test to genotype nondeletional α- and β-thalassemia mutations by an electrochemical DNA sensor. METHODS: Screen-printed electrodes were used as electrochemical transducers for the sensor, in which the capture probe DNA was attached to the golden surface of the working electrode via an S-Au covalent bond, which is highly suitable for immobilizing the biological element...
September 2016: Journal of Clinical Laboratory Analysis
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