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https://www.readbyqxmd.com/read/28930659/group-1-innate-lymphoid-cell-lineage-identity-is-determined-by-a-cis-regulatory-element-marked-by-a-long-non-coding-rna
#1
Walter K Mowel, Sam J McCright, Jonathan J Kotzin, Magalie A Collet, Asli Uyar, Xin Chen, Alexandra DeLaney, Sean P Spencer, Anthony T Virtue, EnJun Yang, Alejandro Villarino, Makoto Kurachi, Margaret C Dunagin, Gretchen Harms Pritchard, Judith Stein, Cynthia Hughes, Diogo Fonseca-Pereira, Henrique Veiga-Fernandes, Arjun Raj, Taku Kambayashi, Igor E Brodsky, John J O'Shea, E John Wherry, Loyal A Goff, John L Rinn, Adam Williams, Richard A Flavell, Jorge Henao-Mejia
Commitment to the innate lymphoid cell (ILC) lineage is determined by Id2, a transcriptional regulator that antagonizes T and B cell-specific gene expression programs. Yet how Id2 expression is regulated in each ILC subset remains poorly understood. We identified a cis-regulatory element demarcated by a long non-coding RNA (lncRNA) that controls the function and lineage identity of group 1 ILCs, while being dispensable for early ILC development and homeostasis of ILC2s and ILC3s. The locus encoding this lncRNA, which we termed Rroid, directly interacted with the promoter of its neighboring gene, Id2, in group 1 ILCs...
September 19, 2017: Immunity
https://www.readbyqxmd.com/read/28922406/loss-of-liver-specific-and-sexually-dimorphic-gene-expression-by-aryl-hydrocarbon-receptor-activation-in-c57bl-6-mice
#2
Rance Nault, Kelly A Fader, Jack R Harkema, Tim Zacharewski
The aryl hydrocarbon receptor (AhR) is a highly conserved transcription factor that mediates a broad spectrum of species-, strain-, sex-, age-, tissue-, and cell-specific responses elicited by structurally diverse ligands including 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Dose-dependent effects on liver-specific and sexually dimorphic gene expression were examined in male and female mice gavaged with TCDD every 4 days for 28 or 92 days. RNA-seq data revealed the coordinated repression of 181 genes predominately expressed in the liver including albumin (3...
2017: PloS One
https://www.readbyqxmd.com/read/28920001/zoledronic-acid-inhibits-nfat-and-il-2-signaling-pathways-in-regulatory-t-cells-and-diminishes-their-suppressive-function-in-patients-with-metastatic-cancer
#3
Dhifaf Sarhan, Caroline Leijonhufvud, Shannon Murray, Kristina Witt, Christina Seitz, Majken Wallerius, Hanjing Xie, Anders Ullén, Ulrika Harmenberg, Elisabet Lidbrink, Charlotte Rolny, John Andersson, Andreas Lundqvist
Regulatory T cells (Treg) suppress anti-tumor immune responses and their infiltration in the tumor microenvironment is associated with inferior prognosis in cancer patients. Thus, in order to enhance anti-tumor immune responses, selective depletion of Treg is highly desired. We found that treatment with zoledronic acid (ZA) resulted in a selective decrease in the frequency of Treg that was associated with a significant increase in proliferation of T cells and natural killer (NK) cells in peripheral blood of patients with metastatic cancer...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28916644/subset-and-tissue-defined-stat5-thresholds-control-homeostasis-and-function-of-innate-lymphoid-cells
#4
Alejandro V Villarino, Giuseppe Sciumè, Fred P Davis, Shigeru Iwata, Beatrice Zitti, Gertraud W Robinson, Lothar Hennighausen, Yuka Kanno, John J O'Shea
Innate lymphoid cells (ILCs) patrol environmental interfaces to defend against infection and protect barrier integrity. Using a genetic tuning model, we demonstrate that the signal-dependent transcription factor (TF) STAT5 is critical for accumulation of all known ILC subsets in mice and reveal a hierarchy of STAT5 dependency for populating lymphoid and nonlymphoid tissues. We apply transcriptome and genomic distribution analyses to define a STAT5 gene signature in natural killer (NK) cells, the prototypical ILC subset, and provide a systems-based molecular rationale for its key functions downstream of IL-15...
September 15, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28916201/targeting-heparanase-to-the-mammary-epithelium-enhances-mammary-gland-development-and-promotes-tumor-growth-and-metastasis
#5
Ilanit Boyango, Uri Barash, Liat Fux, Inna Naroditsky, Neta Ilan, Israel Vlodavsky
Heparanase is an endoglucuronidase that uniquely cleaves the heparan sulfate side chains of heparan sulfate proteoglycans. This activity ultimately alters the structural integrity of the ECM and basement membrane that becomes more prone to cellular invasion by metastatic cancer cells and cells of the immune system. In addition, enzymatically inactive heparanase was found to facilitate the proliferation and survival of cancer cells by activation of signaling molecules such as Akt, Src, signal transducer and activation of transcription (Stat), and epidermal growth factor receptor...
September 12, 2017: Matrix Biology: Journal of the International Society for Matrix Biology
https://www.readbyqxmd.com/read/28914425/platelet-factor-4-increases-bone-marrow-b-cell-development-and-differentiation
#6
David J Field, Angela A Aggrey-Amable, Sara K Blick, Sara K Ture, Andrew Johanson, Scott J Cameron, Sukanya Roy, Craig N Morrell
Platelet factor 4 (PF4) is a megakaryocyte-/platelet-derived chemokine with diverse functions as a regulator of vascular and immune biology. PF4 has a central role in vessel injury responses, innate immune cell responses, and T-helper cell differentiation. We have now discovered that PF4 has a direct role in B cell differentiation in the bone marrow. Mice lacking PF4 (PF4(-/-) mice) had fewer developing B cells in the bone marrow beginning after the pre-pro-B cell stage of differentiation. In vitro, PF4 increased the differentiation of hematopoietic progenitors to B cell lineage cells, indicating that PF4 has a direct effect on B cell differentiation...
September 15, 2017: Immunologic Research
https://www.readbyqxmd.com/read/28913408/hepatocyte-specific-deletion-of-mouse-lamin-a-c-leads-to-male-selective-steatohepatitis
#7
Raymond Kwan, Graham F Brady, Maria Brzozowski, Sujith V Weerasinghe, Hope Martin, Min-Jung Park, Makayla J Brunt, Ram K Menon, Xin Tong, Lei Yin, Colin L Stewart, M Bishr Omary
BACKGROUND & AIMS: Lamins are nuclear intermediate filament proteins that comprise the major components of the nuclear lamina. Mutations in LMNA, which encodes lamins A/C, cause laminopathies, including lipodystrophy, cardiomyopathy, and premature aging syndromes. However, the role of lamins in the liver is unknown, and it is unclear whether laminopathy-associated liver disease is caused by primary hepatocyte defects or systemic alterations. METHODS: To address these questions, we generated mice carrying a hepatocyte-specific deletion of Lmna (knockout [KO] mice) and characterized the KO liver and primary hepatocyte phenotypes by immunoblotting, immunohistochemistry, microarray analysis, quantitative real-time polymerase chain reaction, and Oil Red O and Picrosirius red staining...
November 2017: Cellular and Molecular Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/28912605/peripheral-human-cd4-cd8-t-lymphocytes-exhibit-a-memory-phenotype-and-enhanced-responses-to-il-2-il-7-and-il-15
#8
Marie-Laure Clénet, François Gagnon, Ana Carmena Moratalla, Emilie C Viel, Nathalie Arbour
CD4(+)CD8(+) T lymphocytes account for 1-2% of circulating human T lymphocytes, but their frequency is augmented in several diseases. The phenotypic and functional properties of these T lymphocytes are still ill-defined. We performed an ex vivo characterization of CD4(+)CD8(+) T lymphocytes from the blood of healthy individuals. We observed that CD4(+)CD8(+) T lymphocytes exhibit several characteristics associated with memory T lymphocytes including the expression of chemokine receptors (e.g. CCR7, CXCR3, CCR6) and activation markers (e...
September 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28893433/effects-of-remote-ischemic-preconditioning-in-patients-with-concentric-myocardial-hypertrophy-a-randomized-controlled-trial-with-molecular-insights
#9
Young Song, Jong Wook Song, Sak Lee, Ji-Hae Jun, Young-Lan Kwak, Jae-Kwang Shim
BACKGROUND: Efficacy of remote ischemic preconditioning (RIPC) for cardioprotection in cardiac surgery is controversial. We aimed to evaluate the clinical and molecular effects of RIPC on the concentrically hypertrophied myocardium. METHODS: Seventy-two aortic stenosis patients receiving aortic valve replacement (AVR) under sevoflurane anesthesia were randomly allocated to RIPC (3cycles of 5-min inflation [300mmHg] and deflation on the left arm) or control (deflated cuff placement) group...
September 6, 2017: International Journal of Cardiology
https://www.readbyqxmd.com/read/28887433/the-neurobeachin-like-2-protein-regulates-mast-cell-homeostasis
#10
Sebastian Drube, Randy Grimlowski, Carsten Deppermann, Julia Fröbel, Florian Kraft, Nico Andreas, David Stegner, Jan Dudeck, Franziska Weber, Mandy Rödiger, Christiane Göpfert, Julia Drube, Daniela Reich, Bernhard Nieswandt, Anne Dudeck, Thomas Kamradt
The neurobeachin-like 2 protein (Nbeal2) belongs to the family of beige and Chediak-Higashi (BEACH) domain proteins. Loss-of-function mutations in the human NBEAL2 gene or Nbeal2 deficiency in mice cause gray platelet syndrome, a bleeding disorder characterized by macrothrombocytopenia, splenomegaly, and paucity of α-granules in megakaryocytes and platelets. We found that in mast cells, Nbeal2 regulates the activation of the Shp1-STAT5 signaling axis and the composition of the c-Kit/STAT signalosome. Furthermore, Nbeal2 mediates granule formation and restricts the expression of the transcription factors, IRF8, GATA2, and MITF as well as of the cell-cycle inhibitor p27, which are essential for mast cell differentiation, proliferation, and cytokine production...
September 8, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28881983/a-scalable-moment-closure-approximation-for-large-scale-biochemical-reaction-networks
#11
Atefeh Kazeroonian, Fabian J Theis, Jan Hasenauer
Motivation: Stochastic molecular processes are a leading cause of cell-to-cell variability. Their dynamics are often described by continuous-time discrete-state Markov chains and simulated using stochastic simulation algorithms. As these stochastic simulations are computationally demanding, ordinary differential equation models for the dynamics of the statistical moments have been developed. The number of state variables of these approximating models, however, grows at least quadratically with the number of biochemical species...
July 15, 2017: Bioinformatics
https://www.readbyqxmd.com/read/28867537/thermal-injury-of-the-skin-induces-g-csf-dependent-attenuation-of-epo-mediated-stat-signaling-and-erythroid-differentiation-arrest-in-mice
#12
John G Noel, Benjamin J Ramser, Jose A Cancelas, Francis X McCormack, Jason C Gardner
Inflammation-mediated impairment of erythropoiesis plays a central role in the development of the anemia of critical illness (ACI). ACI develops despite elevation of endogenous erythropoietin (EPO), does not respond to exogenous erythropoietin (EPO) supplementation, and contributes significantly to transfusion requirements in burned patients. We have reported previously that the reduction of red blood cell mass in the bone marrow of a burn-injured ACI mouse model is granulocyte colony-stimulating factor (G-CSF) dependent...
September 1, 2017: Experimental Hematology
https://www.readbyqxmd.com/read/28863322/il-17-contributes-to-the-pathogenesis-of-obliterative-bronchiolitis-via-regulation-of-m1-macrophages-polarization-in-murine-heterotopic-trachea-transplantation-models
#13
Qingshu Meng, Jie Liu, Fang Lin, Luer Bao, Yuyu Jiang, Liang Zheng, Jinjun Tie, Lin Zhang, Xiaoting Liang, Lu Wei, Yuan Li, Huimin Fan, Xiaohui Zhou
Acute allograft rejection is a principal conundrum in lung obliterative bronchiolitis (OB). Monocytes/macrophages infiltration has been proved to be the main reason for acute rejection. IL-17 contributes to the recruitment and function of macrophages. However, the mechanism of IL-17 underlying OB progression remains elusive. In the present study, we showed that the deficiency of IL-17 attenuated the pathology of murine heterotopic trachea allografts. Compared to WT recipients, IL-17(-/-) mice displayed higher frequency of CD206+ cells and lower ratio of CD86+ cells among F4/80+ macrophages in allografts and spleens on day 7 post heterotopic trachea transplantation...
August 29, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28830934/op449-inhibits-breast-cancer-growth-without-adverse-metabolic-effects
#14
Gadi Shlomai, Zara Zelenko, Irini Markella Antoniou, Marilyn Stasinopoulos, Aviva Tobin-Hess, Michael P Vitek, Derek LeRoith, Emily Jane Gallagher
Hyperinsulinemia is associated with a decrease in breast cancer recurrence-free survival and overall survival. Inhibition of insulin receptor signaling is associated with glycemic dysregulation. SET is a direct modulator of PP2A, which negatively regulates the PI3K/AKT/mTOR pathway. OP449, a SET inhibitor, decreases AKT/mTOR activation. The effects of OP449 treatment on breast cancer growth in the setting of pre-diabetes, and its metabolic implications are currently unknown. We found that the volumes and weights of human MDA-MB-231 breast cancer xenografts were greater in hyperinsulinemic mice compared with controls (P < 0...
October 2017: Endocrine-related Cancer
https://www.readbyqxmd.com/read/28816577/coenzyme-q10-inhibits-th17-and-stat3-signaling-pathways-to-ameliorate-colitis-in-mice
#15
Seon-Yeong Lee, Seung Hoon Lee, Eun-Ji Yang, Jae-Kyung Kim, Eun-Kyung Kim, KyungAh Jung, Hongsoon Jung, Kyungjin Lee, Han Hee Lee, Bo-In Lee, Sung-Hwan Park, Dong Yun Shin, Mi-La Cho
Coenzyme Q10 (CoQ10) is a powerful antioxidant substance synthesized in the body. The current study aimed to determine whether CoQ10 suppresses inflammation and inhibits p-STAT3 expression in an experimental colitis mouse model. The mice were orally fed with CoQ10 once a day for 13 days. Histological analysis of the colons was performed by immunohistochemistry. Expression of IL-17, FOXP3, p53, AMPK, and mTOR and activation of p-STAT3 and p-STAT5 in lymph node and spleen tissues were detected by confocal microscopy of stained tissue sections...
September 2017: Journal of Medicinal Food
https://www.readbyqxmd.com/read/28806763/genome-wide-regulation-of-electro-acupuncture-on-the-neural-stat5-loss-induced-obese-mice
#16
Shu-Ping Fu, Hao Hong, Sheng-Feng Lu, Chen-Jun Hu, Hou-Xi Xu, Qian Li, Mei-Ling Yu, Chen Ou, Jian-Zhong Meng, Tian-Lin Wang, Lothar Hennighausen, Bing-Mei Zhu
Acupuncture is reported to be effective in treating obesity related illnesses, but its mechanism is still unclear. To investigate this mechanism we applied electro-acupuncture (EA) in a mouse model of obesity and used RNA-seq to identify molecular consequences. Deletion of the transcription factor STAT5 from neurons (Stat5NKO) led to obesity. Acupuncture, in turn, reduced body weight and the ratio of epididymal white adipose tissue (Epi-WAT) to body weight, and it also decreased plasma concentrations of glucose, triglyceride, and cholesterol...
2017: PloS One
https://www.readbyqxmd.com/read/28802860/upregulation-of-il-9-and-jak-stat-signaling-pathway-in-children-with-autism
#17
Sheikh F Ahmad, Ahmed Nadeem, Mushtaq A Ansari, Saleh A Bakheet, Laila Yousef Al-Ayadhi, Sabry M Attia
Autism spectrum disorder (ASD) gradually develops predominantly neurodevelopmental disorders, which are socially diagnosed in early childhood. Though the etiopathology of ASD is not clear, immune alteration has been suggested as autism's pathophysiological mechanism. Previous studies found that several cytokines and transcription factor activation pathways were significantly increased in ASD. IL-9 has been confirmed to play a significant role in the central nervous system (CNS). The aim of the present study was to investigate the understudied role of pro- and anti-inflammatory cytokines and the JAK-STAT signaling pathway in ASD...
August 9, 2017: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/28798028/ptpn2-regulates-t-cell-lineage-commitment-and-%C3%AE-%C3%AE-versus-%C3%AE-%C3%AE-specification
#18
Florian Wiede, Jarrod A Dudakov, Kun-Hui Lu, Garron T Dodd, Tariq Butt, Dale I Godfrey, Andreas Strasser, Richard L Boyd, Tony Tiganis
In the thymus, hematopoietic progenitors commit to the T cell lineage and undergo sequential differentiation to generate diverse T cell subsets, including major histocompatibility complex (MHC)-restricted αβ T cell receptor (TCR) T cells and non-MHC-restricted γδ TCR T cells. The factors controlling precursor commitment and their subsequent maturation and specification into αβ TCR versus γδ TCR T cells remain unclear. Here, we show that the tyrosine phosphatase PTPN2 attenuates STAT5 (signal transducer and activator of transcription 5) signaling to regulate T cell lineage commitment and SRC family kinase LCK and STAT5 signaling to regulate αβ TCR versus γδ TCR T cell development...
September 4, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28794449/il-7r%C3%AE-glutamylation-and-activation-of-transcription-factor-sall3-promote-group-3-ilc-development
#19
Benyu Liu, Buqing Ye, Xiaoxiao Zhu, Guanling Huang, Liuliu Yang, Pingping Zhu, Ying Du, Jiayi Wu, Shu Meng, Yong Tian, Zusen Fan
Group 3 innate lymphoid cells (ILC3) promote lymphoid organogenesis and potentiate immune responses against bacterial infection. However, how ILC3 cells are developed and maintained is still unclear. Here, we show that carboxypeptidase CCP2 is highly expressed in common helper-like innate lymphoid progenitors, the progenitor of innate lymphoid cells, and CCP2 deficiency increases ILC3 numbers. Interleukin-7 receptor subunit alpha (IL-7Rα) is identified as a substrate of CCP2 for deglutamylation, and IL-7Rα polyglutamylation is catalyzed by polyglutamylases TTLL4 and TTLL13 in common helper-like innate lymphoid progenitors...
August 10, 2017: Nature Communications
https://www.readbyqxmd.com/read/28793932/hydroxychloroquine-inhibits-cd154-expression-in-cd4-t-lymphocytes-of-systemic-lupus-erythematosus-through-nfat-but-not-stat5-signaling
#20
Shu-Fen Wu, Chia-Bin Chang, Jui-Mei Hsu, Ming-Chi Lu, Ning-Sheng Lai, Chin Li, Chien-Hsueh Tung
BACKGROUND: Overexpression of membranous CD154 in T lymphocytes has been found previously in systemic lupus erythematosus (SLE). Because hydroxychloroquine (HCQ) has been used frequently in the treatment of lupus, we sought to identify the effects of HCQ on CD154 and a possibly regulatory mechanism. METHODS: CD4(+) T cells were isolated from the blood of lupus patients. After stimulation with ionomycin or IL-15 and various concentrations of HCQ, expression of membranous CD154 and NFAT and STAT5 signaling were assessed...
August 9, 2017: Arthritis Research & Therapy
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