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https://www.readbyqxmd.com/read/29339496/thymic-stromal-lymphopoietin-drives-the-development-of-il-13-th2-cells
#1
Sotaro Ochiai, Ferdinand Jagot, Ryan L Kyle, Evelyn Hyde, Ruby F White, Melanie Prout, Alfonso J Schmidt, Hidehiro Yamane, Olivier Lamiable, Graham Le Gros, Franca Ronchese
T helper 2 (Th2) cells are pivotal in the development of allergy. Allergen exposure primes IL-4+ Th2 cells in lymph node, but production of effector cytokines including IL-5 and IL-13 is thought to require additional signals from antigen and the environment. Here we report that a substantial proportion of naive CD4+ T cells in spleen and lymph node express receptors for the epithelium-derived inflammatory cytokine thymic stromal lymphopoietin (TSLP). Culture of naive CD4+ T cells in anti-(a)CD3, aCD28, and TSLP-supplemented Th2 conditions enabled the development of a unique population of IL-13-single positive (IL-13-SP) CD4+ T cells; TSLP and Th2 conditions were both required for their development...
January 16, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29326336/arid5b-as-a-critical-downstream-target-of-the-tal1-complex-that-activates-the-oncogenic-transcriptional-program-and-promotes-t-cell-leukemogenesis
#2
Wei Zhong Leong, Shi Hao Tan, Phuong Cao Thi Ngoc, Stella Amanda, Alice Wei Yee Yam, Wei-Siang Liau, Zhiyuan Gong, Lee N Lawton, Daniel G Tenen, Takaomi Sanda
The oncogenic transcription factor TAL1/SCL induces an aberrant transcriptional program in T-cell acute lymphoblastic leukemia (T-ALL) cells. However, the critical factors that are directly activated by TAL1 and contribute to T-ALL pathogenesis are largely unknown. Here, we identified AT-rich interactive domain 5B (ARID5B) as a collaborating oncogenic factor involved in the transcriptional program in T-ALL. ARID5B expression is down-regulated at the double-negative 2-4 stages in normal thymocytes, while it is induced by the TAL1 complex in human T-ALL cells...
January 11, 2018: Genes & Development
https://www.readbyqxmd.com/read/29324237/dna-induction-of-mdm2-promotes-proliferation-of-human-renal-mesangial-cells-and-alters-peripheral-b-cells-subsets-in-pediatric-systemic-lupus-erythematosus
#3
Chen-Xing Zhang, Ji Chen, Li Cai, Jing Wu, Jia-Yuan Wang, Lan-Fang Cao, Wei Zhou, Tong-Xin Chen
The study is aimed to investigate the role of MDM2 in the pathogenesis of lupus nephritis (LN) in pediatric SLE (pSLE). We confirmed that MDM2 expression was increased in peripheral blood mononuclear cells (PBMCs) as well as renal specimen of SLE compared with that of controls by western blot and immunofluorescence staining. Percentage of apoptotic and necrotic CD4+T, CD8+T and B cells were detected by flow cytometry respectively and levels of plasma cell free DNA (cfDNA) were quantified in SLE and healthy controls (HC)...
January 8, 2018: Molecular Immunology
https://www.readbyqxmd.com/read/29323266/aif-loss-deregulates-hematopoiesis-and-reveals-different-adaptive-metabolic-responses-in-bone-marrow-cells-and-thymocytes
#4
Lauriane Cabon, Audrey Bertaux, Marie-Noëlle Brunelle-Navas, Ivan Nemazanyy, Laurianne Scourzic, Laure Delavallée, Laura Vela, Mathieu Baritaud, Sandrine Bouchet, Cécile Lopez, Vu Quang Van, Kevin Garbin, Danielle Chateau, Françoise Gilard, Marika Sarfati, Thomas Mercher, Olivier A Bernard, Santos A Susin
Mitochondrial metabolism is a tightly regulated process that plays a central role throughout the lifespan of hematopoietic cells. Herein, we analyze the consequences of the mitochondrial oxidative phosphorylation (OXPHOS)/metabolism disorder associated with the cell-specific hematopoietic ablation of apoptosis-inducing factor (AIF). AIF-null (AIF-/Y ) mice developed pancytopenia that was associated with hypocellular bone marrow (BM) and thymus atrophy. Although myeloid cells were relatively spared, the B-cell and erythroid lineages were altered with increased frequencies of precursor B cells, pro-erythroblasts I, and basophilic erythroblasts II...
January 11, 2018: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29301945/modulation-of-glutathione-promotes-apoptosis-in-triple-negative-breast-cancer-cells
#5
Tara Miran, Andreas T J Vogg, Natascha Drude, Felix M Mottaghy, Agnieszka Morgenroth
Triple-negative breast cancer has an extremely high rate of relapse. This is particularly due to the existence and survival of cancer stem cells (CSCs) characterized by increased amounts of glutathione (GSH). In this study, we evaluated the potential of pharmacological GSH depletion to sensitize CSCs to ionizing radiotherapy with an I-125-labeled nucleoside analog, 5-iodo-4'-thio-2'-deoxyuridine (ITdU). CSCs were isolated using CD24-- and CD44+-specific microbeads. GSH and reactive oxygen species (ROS) were evaluated by fluorescence-activated cell sorting...
January 4, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29296965/infiltration-of-effector-regulatory-t-cells-predicts-poor-prognosis-of-diffuse-large-b-cell-lymphoma-not-otherwise-specified
#6
Shoko Nakayama, Taiji Yokote, Toshikazu Akioka, Nobuya Hiraoka, Uta Nishiwaki, Takuji Miyoshi, Kazuki Iwaki, Ayami Takayama, Yuki Masuda, Jun Hatooka, Mayumi Fujimoto, Yasuichiro Nishimura, Motomu Tsuji
Regulatory T cells (Tregs) specifically express the transcription factor forkhead box P3 (FOXP3) and contribute to tumor progression. FOXP3-positive cells have been recently proven to be heterogeneous in phenotype and function, including effector Tregs (eTregs), naïve Tregs, and non-Tregs, which harbor no suppressive function. Therefore, it is crucial to investigate the "true Treg (eTreg)" population, rather than the entire FOXP3 population, with regards to their effect on tumor immunity. In particular, in diffuse large B-cell lymphoma, not otherwise specified (DLBCL, NOS), FOXP3-positive cells correlated with a better prognosis...
March 14, 2017: Blood Advances
https://www.readbyqxmd.com/read/29251733/parabiosis-reveals-leukocyte-dynamics-in-the-kidney
#7
Jeremie M Lever, Zhengqin Yang, Ravindra Boddu, Oreoluwa O Adedoyin, Lingling Guo, Reny Joseph, Amie M Traylor, Anupam Agarwal, James F George
The immune cellular compartment of the kidney is involved in organ development and homeostasis, as well as in many pathological conditions. Little is known about the mechanisms that drive intrarenal immune responses in the presence of renal tubular and interstitial cell death. However, it is known that tissue-resident leukocytes have the potential to have distinct roles compared with circulating cells. We used a parabiosis model in C57BL/6 CD45 congenic and green fluorescent protein transgenic mice to better understand the dynamics of immune cells in the kidney...
December 18, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/29167333/authentic-patient-derived-hepatitis-c-virus-infects-and-productively-replicates-in-primary-cd4-and-cd8-t-lymphocytes-in-vitro
#8
Georgia Skardasi, Annie Y Chen, Tomasz I Michalak
Accumulated evidence indicates that immune cells can support replication of hepatitis C virus (HCV) in infected patients and in culture. However, there is a scarcity of data on the degree to which individual immune cell types support HCV propagation and on characteristics of virus assembled. We investigated the ability of authentic, patient-derived HCV to infect in vitro two closely related but functionally distinct immune cell types, CD4+ and CD8+ T lymphocytes, and assessed properties of virus produced by these cells...
November 22, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29164209/tuning-the-cytotoxicity-of-ruthenium-ii-para-cymene-complexes-by-mono-substitution-at-a-triphenylphosphine-phenoxydiphenylphosphine-ligand
#9
Lorenzo Biancalana, Stefano Zacchini, Nicola Ferri, Maria Giovanna Lupo, Guido Pampaloni, Fabio Marchetti
The new complexes [RuCl2(η(6)-p-cymene)(κP-Ph2PR)] [R = 4-C6H4OSiMe2(t)Bu, 1; R = 4-C6H4Br, 2; R = OC([double bond, length as m-dash]O)CHCl2, 3; R = OPh, 4; R = O(2-C6H4SiMe2(t)Bu), 5] and [Ru(C2O4)(η(6)-p-cymene){κP-Ph2PO(2-C6H4(SiMe2(t)Bu))}], 6, were obtained in 83-98% yield from Ru(ii) arene precursors by three different synthetic strategies. The unprecedented phosphine Ph2P(O(2-C6H4SiMe2(t)Bu)) was synthesized in 86% yield from 2-C6H4Br(OSiMe2(t)Bu) and Ph2PCl, via intramolecular oxygen to carbon 1,3 migration of the silyl group (retro-Brook rearrangement)...
November 22, 2017: Dalton Transactions: An International Journal of Inorganic Chemistry
https://www.readbyqxmd.com/read/29162920/the-corepressor-ncor1-regulates-the-survival-of-single-positive-thymocytes
#10
Lena Müller, Daniela Hainberger, Valentina Stolz, Patricia Hamminger, Hammad Hassan, Teresa Preglej, Nicole Boucheron, Shinya Sakaguchi, G Jan Wiegers, Andreas Villunger, Johan Auwerx, Wilfried Ellmeier
Nuclear receptor corepressor 1 (NCOR1) is a transcriptional regulator bridging repressive chromatin modifying enzymes with transcription factors. NCOR1 regulates many biological processes, however its role in T cells is not known. Here we show that Cd4-Cre-mediated deletion of NCOR1 (NCOR1 cKO(Cd4)) resulted in a reduction of peripheral T cell numbers due to a decrease in single-positive (SP) thymocytes. In contrast, double-positive (DP) thymocyte numbers were not affected in the absence of NCOR1. The reduction in SP cells was due to diminished survival of NCOR1-null postselection TCRβ(hi)CD69(+) and mature TCRβ(hi)CD69(-) thymocytes...
November 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29155103/rasgrp1-mutation-in-autoimmune-lymphoproliferative-syndrome-like-disease
#11
Huawei Mao, Wanling Yang, Sylvain Latour, Jing Yang, Sarah Winter, Jian Zheng, Ke Ni, Minmin Lv, Chenjing Liu, Hongmei Huang, Koon-Wing Chan, Pamela Pui-Wah Lee, Wenwei Tu, Alain Fischer, Yu-Lung Lau
BACKGROUND: Autoimmune lymphoproliferative syndrome (ALPS) is a genetic disorder of lymphocyte homeostasis due to impaired apoptosis. It was initially regarded as a very rare disease, but recent studies show it may be more common than previously thought. Defects in a couple of genes have been identified in a proportion of ALPS patients, but around one third of such patients remain undefined genetically. OBJECTIVE: We described two siblings presenting with ALPS-like disease...
November 15, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/29128969/in-vasculitis-of-small-muscular-arteries-activation-of-vessel-infiltrating-cd8-t-cells-seems-to-be-antigen-independent
#12
Mikiko Kobayashi, Eisaku Ogawa, Ryuhei Okuyama, Hiroyuki Kanno
The etiology of polyarteritis nodosa (PAN) and localized PAN is still unknown, although a T cell-mediated immune mechanism has been considered. CD8 T cells participate not only in the antigen-dependent adaptive immune system, but also in the antigen-independent innate immune system. Non-antigen-activated CD8 T cells express a unique phenotype: granzyme B (GrB) positive /CD25 negative /programmed death-1 (PD-1) negative. The aims of this study were to assess the participation of T cells, especially innate CD8 T cells, in the development of vasculitis...
November 11, 2017: Virchows Archiv: An International Journal of Pathology
https://www.readbyqxmd.com/read/29111983/acute-flare-of-bullous-pemphigus-with-pembrolizumab-used-for-treatment-of-metastatic-urothelial-cancer
#13
Rohan Garje, Justin J Chau, Jina Chung, Karolyn Wanat, Yousef Zakharia
In the past decade, the resurgence of immunotherapy has changed the landscape of cancer therapy. Checkpoint inhibitors targeting cytotoxic T-lymphocyte antigen-4, programmed death-1 on lymphocytes, and programmed death ligand-1 on tumors cells are currently utilized in the management of several cancers. These agents are double-edged sword with the positive effect being robust antitumor response but on the other side they can throttle up the normal immunologic homeostasis in a negative way, leading to adverse autoimmune toxicities...
November 3, 2017: Journal of Immunotherapy
https://www.readbyqxmd.com/read/29105157/reduced-numbers-of-mature-medullary-thymic-epithelial-cells-in-skg-mice
#14
Robby Engelmann, Andra Biemelt, Anja Johl, Daniela Kuthning, Brigitte Müller-Hilke
Attenuated T cell receptor (TCR) signaling contributes to the susceptibility for autoimmunity as shown via mutants of PTPN22 and Zap70 genes. We here set out to investigate the effect of an attenuated TCR signal on the composition of the thymic epithelial cell (TEC) compartment. To that extent, we combined flow cytometry and histology and compared the TEC subpopulations of Zap70 wild type with SKG mutant mice. We found an increased cortical TEC compartment in SKG thymi at the expense of reduced numbers of mature medullary TECs and a 4...
November 3, 2017: Scandinavian Journal of Immunology
https://www.readbyqxmd.com/read/29099628/murine-cd8-invariant-natural-killer-t-cells-are-negatively-selected-by-cd1d-expressed-on-thymic-epithelial-cells-and-dendritic-cells
#15
Sejin Oh, Hyunji Lee, Jung Hoon Shin, Changwan Hong, Se-Ho Park
BACKGROUND: CD1d-dependent invariant natural killer (iNKT) cells are found as either CD4 single positive (SP) or CD4/CD8 double negative (DN) cells in mice. The size of the CD8(+) iNKT population is extremely small. It is known that CD1d expression on developing thymocytes is sufficient for iNKT development and co-receptor choice, which is driven by Th-POK expression. This study aimed to examine the factors involved in the CD4/CD8 co-receptor choice of iNKT cells in addition to Th-POK-driven silencing of CD8 expression...
November 3, 2017: Immunological Investigations
https://www.readbyqxmd.com/read/29096894/experimental-therapy-of-advanced-breast-cancer-targeting-nfat1-mdm2-p53-pathway
#16
Jiang-Jiang Qin, Wei Wang, Ruiwen Zhang
Advanced breast cancer, especially advanced triple-negative breast cancer, is typically more aggressive and more difficult to treat than other breast cancer phenotypes. There is currently no curable option for breast cancer patients with advanced diseases, highlighting the urgent need for novel treatment strategies. We have recently discovered that the nuclear factor of activated T cells 1 (NFAT1) activates the murine double minute 2 (MDM2) oncogene. Both MDM2 and NFAT1 are overexpressed and constitutively activated in breast cancer, particularly in advanced breast cancer, and contribute to its initiation, progression, and metastasis...
2017: Progress in Molecular Biology and Translational Science
https://www.readbyqxmd.com/read/29091262/isolation-and-functional-use-of-human-nkt-cells
#17
Mark A Exley, S Brian Wilson, Steven P Balk
This unit details methods for the isolation, in vitro expansion, and functional characterization of human iNKT cells. The term 'iNKT' derives from the fact that a large fraction of murine and some human NK marker+ T cells ('NKT') recognize the MHC class I-like CD1d protein and use an identical 'invariant' TCRα chain, which is generated in humans by precise Vα24 and Jα18 rearrangements with either no N-region diversity or subsequent trimming to identical or nearly identical amino acid sequence (hence, 'iNKT' cells)...
November 1, 2017: Current Protocols in Immunology
https://www.readbyqxmd.com/read/29081196/-prognostic-significance-of-proteins-expression-by-immunohistochemical-method-in-diffuse-large-b-cell-lymphoma
#18
W J Yu, L H Cao, J H Wang, Z M Wang, W B Qian, H Y Tong, H T Meng, W Y Mai, L P Mao, J J Qian, J Jin
Objective: To analyze the prognostic significance of TP53, Bcl-2, Bcl-6, Myc proteins expression by immunohistochemical method (IHC) in diffuse large B cell Lymphoma (DLBCL) . Methods: Clinical and pathologic data of 223 patients with DLBCL hospitalized in Zhejiang First Hospital from March 2009 to June 2015 were retrospectively analyzed. Results: The 223 cases, a median age of 56 years old with a male predominance, had shown a 39.0% of TP53 positive expression, 38.6% of Myc, 69.1% of Bcl-2, 56.5% of Bcl-6, and 22...
September 14, 2017: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
https://www.readbyqxmd.com/read/29079307/circulating-t-cell-subsets-monocytes-and-natural-killer-cells-in-peripartum-cardiomyopathy-results-from-the-multicenter-ipac-study
#19
Charles F McTiernan, Penelope Morel, Leslie T Cooper, Navin Rajagopalan, Vinay Thohan, Mark Zucker, John Boehmer, Biykem Bozkurt, Paul Mather, John Thornton, Jalal K Ghali, Karen Hanley-Yanez, James Fett, Indrani Halder, Dennis M McNamara
OBJECTIVE: Evaluate the hypothesis that the distribution of circulating immune cell subsets, or their activation state, is significantly different between PPCM and healthy postpartum (HP) women. BACKGROUND: Peripartum cardiomyopathy (PPCM) is a major cause of maternal morbidity and mortality and an immune-mediated etiology has been hypothesized. Cellular immunity, altered in pregnancy and the peripartum period, has been proposed to play a role in PPCM pathogenesis...
October 24, 2017: Journal of Cardiac Failure
https://www.readbyqxmd.com/read/29074605/allogeneic-human-double-negative-t-cells-as-a-novel-immunotherapy-for-acute-myeloid-leukemia-and-its-underlying-mechanisms
#20
Jong Bok Lee, Mark D Minden, Weihsu C Chen, Elena Streck, Branson Chen, Hyeonjeong Kang, Andrea Arruda, Dalam Ly, Sandy D Der, Sohyeong Kang, Paulina Achita, Cheryl D'Souza, Yueyang Li, Richard W Childs, John E Dick, Li Zhang
PURPOSE: To explore the potential of ex vivo expanded healthy donor derived allogeneic CD4 and CD8 double negative cells (DNTs) as a novel cellular immunotherapy for leukemia patients. EXPERIMENTAL DESIGN: Clinical grade DNTs from peripheral blood of healthy donors were expanded and their anti-leukemic activity and safety were examined using flow-cytometry based in vitro killing assays and xenograft models against AML patient blasts and healthy donor-derived hematopoietic cells...
October 26, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
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