HOXA9 Cooperates with Activated JAK/STAT Signaling to Drive Leukemia Development
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Limited Presence of IL-22 Binding Protein, a Natural IL-22 Inhibitor, Strengthens Psoriatic Skin Inflammation
Limited Presence of IL-22 Binding Protein, a Natural IL-22 Inhibitor, Strengthens Psoriatic Skin Inflammation This information is current as Jérôme C. Martin, Kerstin Wolk, Gaëlle Bériou, Ahmed of September 25, 2021. Abidi, Ellen Witte-Händel, Cédric Louvet, Georgios Kokolakis, Lucile Drujont, Laure Dumoutier, Jean-Christophe Renauld, Robert Sabat and Régis Josien J Immunol 2017; 198:3671-3678; Prepublished online 29 March 2017; Downloaded from doi: 10.4049/jimmunol.1700021 http://www.jimmunol.org/content/198/9/3671 References This article cites 47 articles, 12 of which you can access for free at: http://www.jimmunol.org/ http://www.jimmunol.org/content/198/9/3671.full#ref-list-1 Why The JI? Submit online. • Rapid Reviews! 30 days* from submission to initial decision • No Triage! Every submission reviewed by practicing scientists by guest on September 25, 2021 • Fast Publication! 4 weeks from acceptance to publication *average Subscription Information about subscribing to The Journal of Immunology is online at: http://jimmunol.org/subscription Permissions Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html Email Alerts Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts The Journal of Immunology is published twice each month by The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 2017 by The American Association of Immunologists, Inc. All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. The Journal of Immunology Limited Presence of IL-22 Binding Protein, a Natural IL-22 Inhibitor, Strengthens Psoriatic Skin Inflammation Je´roˆme C. -
Promoter Janus Kinase 3 Proximal Characterization and Analysis Of
The Journal of Immunology Characterization and Analysis of the Proximal Janus Kinase 3 Promoter1 Martin Aringer,2*† Sigrun R. Hofmann,2* David M. Frucht,* Min Chen,* Michael Centola,* Akio Morinobu,* Roberta Visconti,* Daniel L. Kastner,* Josef S. Smolen,† and John J. O’Shea3* Janus kinase 3 (Jak3) is a nonreceptor tyrosine kinase essential for signaling via cytokine receptors that comprise the common ␥-chain (␥c), i.e., the receptors for IL-2, IL-4, IL-7, IL-9, IL-15, and IL-21. Jak3 is preferentially expressed in hemopoietic cells and is up-regulated upon cell differentiation and activation. Despite the importance of Jak3 in lymphoid development and immune function, the mechanisms that govern its expression have not been defined. To gain insight into this issue, we set out to characterize the Jak3 promoter. The 5-untranslated region of the Jak3 gene is interrupted by a 3515-bp intron. Upstream of this intron and the transcription initiation site, we identified an ϳ1-kb segment that exhibited lymphoid-specific promoter activity and was responsive to TCR signals. Truncation of this fragment revealed that core promoter activity resided in a 267-bp fragment that contains putative Sp-1, AP-1, Ets, Stat, and other binding sites. Mutation of the AP-1 sites significantly diminished, whereas mutation of the Ets sites abolished, the inducibility of the promoter construct. Chromatin immunoprecipitation assays showed that histone acetylation correlates with mRNA expression and that Ets-1/2 binds this region. Thus, transcription factors that bind these sites, especially Ets family members, are likely to be important regulators of Jak3 expression. -
Microglia Emerge from Erythromyeloid Precursors Via Pu.1- and Irf8-Dependent Pathways
ART ic LE S Microglia emerge from erythromyeloid precursors via Pu.1- and Irf8-dependent pathways Katrin Kierdorf1,2, Daniel Erny1, Tobias Goldmann1, Victor Sander1, Christian Schulz3,4, Elisa Gomez Perdiguero3,4, Peter Wieghofer1,2, Annette Heinrich5, Pia Riemke6, Christoph Hölscher7,8, Dominik N Müller9, Bruno Luckow10, Thomas Brocker11, Katharina Debowski12, Günter Fritz1, Ghislain Opdenakker13, Andreas Diefenbach14, Knut Biber5,15, Mathias Heikenwalder16, Frederic Geissmann3,4, Frank Rosenbauer6 & Marco Prinz1,17 Microglia are crucial for immune responses in the brain. Although their origin from the yolk sac has been recognized for some time, their precise precursors and the transcription program that is used are not known. We found that mouse microglia were derived from primitive c-kit+ erythromyeloid precursors that were detected in the yolk sac as early as 8 d post conception. + lo − + − + These precursors developed into CD45 c-kit CX3CR1 immature (A1) cells and matured into CD45 c-kit CX3CR1 (A2) cells, as evidenced by the downregulation of CD31 and concomitant upregulation of F4/80 and macrophage colony stimulating factor receptor (MCSF-R). Proliferating A2 cells became microglia and invaded the developing brain using specific matrix metalloproteinases. Notably, microgliogenesis was not only dependent on the transcription factor Pu.1 (also known as Sfpi), but also required Irf8, which was vital for the development of the A2 population, whereas Myb, Id2, Batf3 and Klf4 were not required. Our data provide cellular and molecular insights into the origin and development of microglia. Microglia are the tissue macrophages of the brain and scavenge dying have the ability to give rise to microglia and macrophages in vitro cells, pathogens and molecules using pattern recognition receptors and in vivo under defined conditions. -
Characterization of a Pediatric T-Cell Acute Lymphoblastic Leukemia Patient with Simultaneous LYL1 and LMO2 Rearrangements
View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Erasmus University Digital Repository Articles and Brief Reports Acute Lymphoblastic Leukemia Characterization of a pediatric T-cell acute lymphoblastic leukemia patient with simultaneous LYL1 and LMO2 rearrangements Irene Homminga, 1 Maartje J. Vuerhard, 1 Anton W. Langerak, 2 Jessica Buijs-Gladdines, 1 Rob Pieters, 1 and Jules P.P. Meijerink 1 1Department of Pediatric Oncology/Hematology, Erasmus MC/Sophia Children’s Hospital, Rotterdam; and 2Department of Immunology, Erasmus MC, Rotterdam, The Netherlands ABSTRACT Translocation of the LYL1 oncogene are rare in T-cell acute consistently clustered along with cases having TAL1 or lymphoblastic leukemia, whereas the homologous TAL1 LMO2 rearrangements. Therefore, LYL1 -rearranged cases are gene is rearranged in approximately 20% of patients. not necessarily associated with immature T-cell develop - Previous gene-expression studies have identified an imma - ment, despite high LYL1 levels, but elicit a TALLMO expres - ture T-cell acute lymphoblastic leukemia subgroup with high sion signature. LYL1 expression in the absence of chromosomal aberrations. Molecular characterization of a t(7;19)(q34;p13) in a pediatric Key words: T-ALL, pediatric, LYL1, LMO2, rearrangements. T-cell acute lymphoblastic leukemia patient led to the identi - fication of a translocation between the TRB@ and LYL1 loci. Citation: Homminga I, Vuerhard MJ, Langerak AW, Buijs- Similar to incidental T-cell acute lymphoblastic leukemia Gladdines J, Pieters R, and Meijerink JPP. Characterization of a cases with synergistic, double translocations affecting pediatric T-cell acute lymphoblastic leukemia patient with simul - TAL1/2 and LMO1/2 oncogenes, this LYL1 -translocated taneous LYL1 and LMO2 rearrangements. -
Supplementary Material
Coagulation & Its Disorders SUPPLEMENTARY APPENDIX Dexamethasone promotes durable factor VIII-specific tolerance in hemophilia A mice via thymic mechanisms Maria T. Georgescu, 1 Paul C. Moorehead, 2,3 Alice S. van Velzen, 4 Kate Nesbitt, 1 Birgit M. Reipert, 5 Katharina N. Steinitz, 5 Maria Schuster, 5 Christine Hough 1 and David Lillicrap 1 1Department of Pathology and Molecular Medicine, Queen’s University, Kingston, ON, Canada; 2Janeway Children’s Health and Reha - bilitation Centre, St. John’s, NL, Canada; 3Faculty of Medicine, Memorial University, St. John’s, NL, Canada; 4Department of Pediatric Hematology, Immunology and Infectious Diseases, Emma Children’s Hospital, Amsterdam, the Netherlands and 5Baxalta Innovations GmbH, Vienna, Austria ©2018 Ferrata Storti Foundation. This is an open-access paper. doi:10.3324/haematol. 2018.189852 Received: January 30, 2018. Accepted: April 19, 2018. Pre-published: April 19, 2018. Correspondence: [email protected] Supplementary Material 100 80 60 40 20 Anti-VWF IgG Positive IgG Mice (%)Anti-VWF 0 FVIII/FVIII FVIII+Dex/FVIII FVIII+Dex/intFVIII+FVIII n=4 n=13 n=12 Figure S1. Administration of Dex during initial FVIII exposure does not impair the immune response to VWF. Anti-VWF IgG incidence at week 22, following exposure to VWF (Week 18-21) in mice initially treated with FVIII or FVIII+Dex and with no evidence of anti-FVIII IgG at week 4. Table S1. Genes down-regulated following FVIII+Dex treatment. Transcript Count Ratio Gene Name FVIII+Dex vs FVIII Dex vs HBSS Ccr4 -5.82 -14.45 Rag1 -4.18 -16.00 Cd69 -3.51 -4.40 Ccr9 -3.46 -9.90 Slamf1 -3.20 -6.50 Cd8b1 -3.18 -7.77 Cd40lg -2.99 -2.56 Cxcl1 -2.90 -2.37 Rag2 -2.84 -9.21 Rorc -2.78 -5.65 Cd8a -2.67 -7.74 Cd4 -2.66 -5.06 Il9 -2.64 -2.26 Il12b -2.60 -2.49 Bcl6 -2.59 -3.30 Il27 -2.54 -3.06 Mr1 -2.48 -3.26 Sh2d1a -2.39 -6.68 Il13 -2.23 -2.38 Ccl22 -2.22 -2.51 Il16 -2.22 -3.05 Socs1 -2.20 -4.55 Card9 -2.12 -3.32 Cxcr4 -2.12 -3.98 Tcf7 -2.12 -5.16 Lck -2.06 -4.47 Icam2 -2.02 -3.09 Table S2. -
Molecular Profile of Tumor-Specific CD8+ T Cell Hypofunction in a Transplantable Murine Cancer Model
Downloaded from http://www.jimmunol.org/ by guest on September 25, 2021 T + is online at: average * The Journal of Immunology , 34 of which you can access for free at: 2016; 197:1477-1488; Prepublished online 1 July from submission to initial decision 4 weeks from acceptance to publication 2016; doi: 10.4049/jimmunol.1600589 http://www.jimmunol.org/content/197/4/1477 Molecular Profile of Tumor-Specific CD8 Cell Hypofunction in a Transplantable Murine Cancer Model Katherine A. Waugh, Sonia M. Leach, Brandon L. Moore, Tullia C. Bruno, Jonathan D. Buhrman and Jill E. Slansky J Immunol cites 95 articles Submit online. Every submission reviewed by practicing scientists ? is published twice each month by Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts http://jimmunol.org/subscription Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html http://www.jimmunol.org/content/suppl/2016/07/01/jimmunol.160058 9.DCSupplemental This article http://www.jimmunol.org/content/197/4/1477.full#ref-list-1 Information about subscribing to The JI No Triage! Fast Publication! Rapid Reviews! 30 days* Why • • • Material References Permissions Email Alerts Subscription Supplementary The Journal of Immunology The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 2016 by The American Association of Immunologists, Inc. All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. This information is current as of September 25, 2021. The Journal of Immunology Molecular Profile of Tumor-Specific CD8+ T Cell Hypofunction in a Transplantable Murine Cancer Model Katherine A. -
IL-22 Binding Protein Promotes the Disease Process in Multiple Sclerosis Hannes Lindahl, André O
IL-22 Binding Protein Promotes the Disease Process in Multiple Sclerosis Hannes Lindahl, André O. Guerreiro-Cacais, Sahl Khalid Bedri, Mathias Linnerbauer, Magdalena Lindén, Nada This information is current as Abdelmagid, Karolina Tandre, Claire Hollins, Lorraine of September 24, 2021. Irving, Colin Glover, Clare Jones, Lars Alfredsson, Lars Rönnblom, Ingrid Kockum, Mohsen Khademi, Maja Jagodic and Tomas Olsson J Immunol published online 10 July 2019 Downloaded from http://www.jimmunol.org/content/early/2019/07/09/jimmun ol.1900400 Supplementary http://www.jimmunol.org/content/suppl/2019/07/10/jimmunol.190040 http://www.jimmunol.org/ Material 0.DCSupplemental Why The JI? Submit online. • Rapid Reviews! 30 days* from submission to initial decision • No Triage! Every submission reviewed by practicing scientists by guest on September 24, 2021 • Fast Publication! 4 weeks from acceptance to publication *average Subscription Information about subscribing to The Journal of Immunology is online at: http://jimmunol.org/subscription Permissions Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html Email Alerts Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts The Journal of Immunology is published twice each month by The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 2019 by The American Association of Immunologists, Inc. All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. Published -
Cytokine Nomenclature
RayBiotech, Inc. The protein array pioneer company Cytokine Nomenclature Cytokine Name Official Full Name Genbank Related Names Symbol 4-1BB TNFRSF Tumor necrosis factor NP_001552 CD137, ILA, 4-1BB ligand receptor 9 receptor superfamily .2. member 9 6Ckine CCL21 6-Cysteine Chemokine NM_002989 Small-inducible cytokine A21, Beta chemokine exodus-2, Secondary lymphoid-tissue chemokine, SLC, SCYA21 ACE ACE Angiotensin-converting NP_000780 CD143, DCP, DCP1 enzyme .1. NP_690043 .1. ACE-2 ACE2 Angiotensin-converting NP_068576 ACE-related carboxypeptidase, enzyme 2 .1 Angiotensin-converting enzyme homolog ACTH ACTH Adrenocorticotropic NP_000930 POMC, Pro-opiomelanocortin, hormone .1. Corticotropin-lipotropin, NPP, NP_001030 Melanotropin gamma, Gamma- 333.1 MSH, Potential peptide, Corticotropin, Melanotropin alpha, Alpha-MSH, Corticotropin-like intermediary peptide, CLIP, Lipotropin beta, Beta-LPH, Lipotropin gamma, Gamma-LPH, Melanotropin beta, Beta-MSH, Beta-endorphin, Met-enkephalin ACTHR ACTHR Adrenocorticotropic NP_000520 Melanocortin receptor 2, MC2-R hormone receptor .1 Activin A INHBA Activin A NM_002192 Activin beta-A chain, Erythroid differentiation protein, EDF, INHBA Activin B INHBB Activin B NM_002193 Inhibin beta B chain, Activin beta-B chain Activin C INHBC Activin C NM005538 Inhibin, beta C Activin RIA ACVR1 Activin receptor type-1 NM_001105 Activin receptor type I, ACTR-I, Serine/threonine-protein kinase receptor R1, SKR1, Activin receptor-like kinase 2, ALK-2, TGF-B superfamily receptor type I, TSR-I, ACVRLK2 Activin RIB ACVR1B -
Homeobox Gene Expression Profile in Human Hematopoietic Multipotent
Leukemia (2003) 17, 1157–1163 & 2003 Nature Publishing Group All rights reserved 0887-6924/03 $25.00 www.nature.com/leu Homeobox gene expression profile in human hematopoietic multipotent stem cells and T-cell progenitors: implications for human T-cell development T Taghon1, K Thys1, M De Smedt1, F Weerkamp2, FJT Staal2, J Plum1 and G Leclercq1 1Department of Clinical Chemistry, Microbiology and Immunology, Ghent University Hospital, Ghent, Belgium; and 2Department of Immunology, Erasmus Medical Center, Rotterdam, The Netherlands Class I homeobox (HOX) genes comprise a large family of implicated in this transformation proces.14 The HOX-C locus transcription factors that have been implicated in normal and has been primarily implicated in lymphomas.15 malignant hematopoiesis. However, data on their expression or function during T-cell development is limited. Using degener- Hematopoietic cells are derived from stem cells that reside in ated RT-PCR and Affymetrix microarray analysis, we analyzed fetal liver (FL) in the embryo and in the adult bone marrow the expression pattern of this gene family in human multipotent (ABM), which have the unique ability to self-renew and thereby stem cells from fetal liver (FL) and adult bone marrow (ABM), provide a life-long supply of blood cells. T lymphocytes are a and in T-cell progenitors from child thymus. We show that FL specific type of hematopoietic cells that play a major role in the and ABM stem cells are similar in terms of HOX gene immune system. They develop through a well-defined order of expression, but significant differences were observed between differentiation steps in the thymus.16 Several transcription these two cell types and child thymocytes. -
Transcriptional Control of Tissue-Resident Memory T Cell Generation
Transcriptional control of tissue-resident memory T cell generation Filip Cvetkovski Submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy in the Graduate School of Arts and Sciences COLUMBIA UNIVERSITY 2019 © 2019 Filip Cvetkovski All rights reserved ABSTRACT Transcriptional control of tissue-resident memory T cell generation Filip Cvetkovski Tissue-resident memory T cells (TRM) are a non-circulating subset of memory that are maintained at sites of pathogen entry and mediate optimal protection against reinfection. Lung TRM can be generated in response to respiratory infection or vaccination, however, the molecular pathways involved in CD4+TRM establishment have not been defined. Here, we performed transcriptional profiling of influenza-specific lung CD4+TRM following influenza infection to identify pathways implicated in CD4+TRM generation and homeostasis. Lung CD4+TRM displayed a unique transcriptional profile distinct from spleen memory, including up-regulation of a gene network induced by the transcription factor IRF4, a known regulator of effector T cell differentiation. In addition, the gene expression profile of lung CD4+TRM was enriched in gene sets previously described in tissue-resident regulatory T cells. Up-regulation of immunomodulatory molecules such as CTLA-4, PD-1, and ICOS, suggested a potential regulatory role for CD4+TRM in tissues. Using loss-of-function genetic experiments in mice, we demonstrate that IRF4 is required for the generation of lung-localized pathogen-specific effector CD4+T cells during acute influenza infection. Influenza-specific IRF4−/− T cells failed to fully express CD44, and maintained high levels of CD62L compared to wild type, suggesting a defect in complete differentiation into lung-tropic effector T cells. -
The Role of Noncoding Mutations in Blood Cancers Sunniyat Rahman and Marc R
© 2019. Published by The Company of Biologists Ltd | Disease Models & Mechanisms (2019) 12, dmm041988. doi:10.1242/dmm.041988 REVIEW The role of noncoding mutations in blood cancers Sunniyat Rahman and Marc R. Mansour* ABSTRACT survival in adult acute myeloid leukaemia (AML) and ALL are The search for oncogenic mutations in haematological malignancies still less than 50%, with significant treatment challenges including has largely focused on coding sequence variants. These variants treatment-resistant disease, clonal heterogeneity of the underlying have been critical in understanding these complex cancers in greater disease, treatment-associated toxicities and poor tolerance for detail, ultimately leading to better disease monitoring, subtyping and intensive treatment regimens, particularly in older patients with prognostication. In contrast, the search for oncogenic variants in the comorbidities (Kansagra et al., 2018). Because of this, there is a noncoding genome has proven to be challenging given the vastness significant impetus to discover new genetic aberrations, including of the search space, the intrinsic difficulty in assessing the impact of driver mutations (see Box 1 for a glossary of terms), that may variants that do not code for functional proteins, and our still primitive provide insight into the mechanisms of malignant haematopoiesis, understanding of the function harboured by large parts of the as well as offering novel therapeutic opportunities. noncoding genome. Recent studies have broken ground on this Detailed genetic characterisation of haematological malignancies quest, identifying somatically acquired and recurrent mutations in the has already identified alterations that are now being used for better noncoding genome that activate the expression of proto-oncogenes. diagnosis, prognostication, subtype identification and to inform In this Review, we explore some of the best-characterised examples therapeutic decisions (Taylor et al., 2017). -
Biomarker Testing in Non- Small Cell Lung Cancer (NSCLC)
The biopharma business of Merck KGaA, Darmstadt, Germany operates as EMD Serono in the U.S. and Canada. Biomarker testing in non- small cell lung cancer (NSCLC) Copyright © 2020 EMD Serono, Inc. All rights reserved. US/TEP/1119/0018(1) Lung cancer in the US: Incidence, mortality, and survival Lung cancer is the second most common cancer diagnosed annually and the leading cause of mortality in the US.2 228,820 20.5% 57% Estimated newly 5-year Advanced or 1 survival rate1 metastatic at diagnosed cases in 2020 diagnosis1 5.8% 5-year relative 80-85% 2 135,720 survival with NSCLC distant disease1 Estimated deaths in 20201 2 NSCLC, non-small cell lung cancer; US, United States. 1. National Institutes of Health (NIH), National Cancer Institute. Cancer Stat Facts: Lung and Bronchus Cancer website. www.seer.cancer.gov/statfacts/html/lungb.html. Accessed May 20, 2020. 2. American Cancer Society. What is Lung Cancer? website. https://www.cancer.org/cancer/non-small-cell-lung-cancer/about/what-is-non-small-cell-lung-cancer.html. Accessed May 20, 2020. NSCLC is both histologically and genetically diverse 1-3 NSCLC distribution by histology Prevalence of genetic alterations in NSCLC4 PTEN 10% DDR2 3% OTHER 25% PIK3CA 12% LARGE CELL CARCINOMA 10% FGFR1 20% SQUAMOUS CELL CARCINOMA 25% Oncogenic drivers in adenocarcinoma Other or ADENOCARCINOMA HER2 1.9% 40% KRAS 25.5% wild type RET 0.7% 55% NTRK1 1.7% ROS1 1.7% Oncogenic drivers in 0% 20% 40% 60% RIT1 2.2% squamous cell carcinoma Adenocarcinoma DDR2 2.9% Squamous cell carcinoma NRG1 3.2% Large cell carcinoma