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DevoTed_miR SIGNED

MicroRNA determinants of the balance between effector and regulatory T cells in vivo

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EC-Contrib. €

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 DevoTed_miR project word cloud

Explore the words cloud of the DevoTed_miR project. It provides you a very rough idea of what is the project "DevoTed_miR" about.

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Project "DevoTed_miR" data sheet

The following table provides information about the project.

Coordinator
INSTITUTO DE MEDICINA MOLECULAR JOAO LOBO ANTUNES 

Organization address
address: AVENIDA PROF EGAS MONIZ
city: LISBOA
postcode: 1649 028
website: www.imm.ul.pt

contact info
title: n.a.
name: n.a.
surname: n.a.
function: n.a.
email: n.a.
telephone: n.a.
fax: n.a.

 Coordinator Country Portugal [PT]
 Project website https://imm.medicina.ulisboa.pt/pt/investigacao/laboratorios/silva-santos-bruno-lab/
 Total cost 2˙000˙000 €
 EC max contribution 2˙000˙000 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2014-CoG
 Funding Scheme ERC-COG
 Starting year 2015
 Duration (year-month-day) from 2015-07-01   to  2020-12-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    INSTITUTO DE MEDICINA MOLECULAR JOAO LOBO ANTUNES PT (LISBOA) coordinator 2˙000˙000.00

Map

 Project objective

T lymphocytes display potent pro- or anti-inflammatory properties, which typically associate with distinct effector (Teff) versus regulatory (Treg) cell subsets. Based on published and our preliminary data showing a major impact of microRNAs on T cell differentiation and (auto)immune pathology, my proposal aims to dissect the miRNA networks that control the balance between Teff and Treg subsets in vivo, in various experimental models of infection and autoimmunity.

We will focus on three critical mediators of T cell functions: interferon-gamma (IFN-g) and interleukin-17A (IL-17), highly pro-inflammatory Teff cytokines; and Foxp3, the transcription factor that confers Treg suppressive properties. To track the activity of these key genes, we will generate a new Ifng/ Il17/ Foxp3 triple reporter mouse, from which we will isolate Teff and Treg subsets to determine their genome-wide miRNA profiles and specific signatures in vivo. We will investigate both natural (thymic-derived and present in naïve mice) and induced (in the periphery upon challenge) Teff and Treg subsets, as they make distinct contributions to the immune response. We will identify miRNAs selectively expressed in Teff (Ifng or Il17) versus Treg (Foxp3) subsets of various lineages (CD4, CD8, gamma-delta or NKT) in each in vivo model; assess whether they are induced during thymic development or upon peripheral activation; and determine the robustness of subset-specific miRNA profiles across various in vivo challenges.

We will then use loss- and gain-of-function strategies to define the individual miRNAs that impact Teff or Treg differentiation and disease pathogenesis; dissect the external cues and intracellular mechanisms that regulate miRNA expression; and identify the mRNA networks controlled by key miRNAs in Teff and Treg differentiation. I expect this project to provide major conceptual and experimental advances towards manipulating miRNAs either to boost immunity or to treat autoimmunity.

 Publications

year authors and title journal last update
List of publications.
2019 Bruno Silva-Santos, Sofia Mensurado, Seth B. Coffelt
γδ T cells: pleiotropic immune effectors with therapeutic potential in cancer
published pages: 392-404, ISSN: 1474-175X, DOI: 10.1038/s41568-019-0153-5
Nature Reviews Cancer 19/7 2020-01-24
2019 Francisco Caiado, Diogo Maia-Silva, Carolina Jardim, Nina Schmolka, Tânia Carvalho, Cláudia Reforço, Rita Faria, Branka Kolundzija, André E. Simões, Tuncay Baubec, Christopher R. Vakoc, Maria Gomes da Silva, Markus G. Manz, Ton N. Schumacher, Håkan Norell, Bruno Silva-Santos
Lineage tracing of acute myeloid leukemia reveals the impact of hypomethylating agents on chemoresistance selection
published pages: , ISSN: 2041-1723, DOI: 10.1038/s41467-019-12983-z
Nature Communications 10/1 2020-01-24
2019 Julie C. Ribot, Rita Neres, Vanessa Zuzarte-Luís, Anita Q. Gomes, Liliana Mancio-Silva, Sofia Mensurado, Daniel Pinto-Neves, Miguel M. Santos, Tânia Carvalho, Jonathan J. M. Landry, Eva A. Rolo, Ankita Malik, Daniel Varón Silva, Maria M. Mota, Bruno Silva-Santos, Ana Pamplona
γδ-T cells promote IFN-γ–dependent Plasmodium pathogenesis upon liver-stage infection
published pages: 201814440, ISSN: 0027-8424, DOI: 10.1073/pnas.1814440116
Proceedings of the National Academy of Sciences 2020-01-24
2019 Miguel Ribeiro, Helena C. Brigas, Mariana Temido-Ferreira, Paula A. Pousinha, Tommy Regen, Cátia Santa, Joana E. Coelho, Inês Marques-Morgado, Cláudia A. Valente, Sara Omenetti, Brigitta Stockinger, Ari Waisman, Bruno Manadas, Luísa V. Lopes, Bruno Silva-Santos, Julie C. Ribot
Meningeal γδ T cell–derived IL-17 controls synaptic plasticity and short-term memory
published pages: eaay5199, ISSN: 2470-9468, DOI: 10.1126/sciimmunol.aay5199
Science Immunology 4/40 2020-01-24
2016 A. R. Almeida, D. V. Correia, A. Fernandes-Platzgummer, C. L. da Silva, M. G. da Silva, D. R. Anjos, B. Silva-Santos
Delta One T Cells for Immunotherapy of Chronic Lymphocytic Leukemia: Clinical-Grade Expansion/Differentiation and Preclinical Proof of Concept
published pages: 5795-5804, ISSN: 1078-0432, DOI: 10.1158/1078-0432.ccr-16-0597
Clinical Cancer Research 22/23 2020-01-24
2018 Sofia Mensurado, Margarida Rei, Telma Lança, Marianna Ioannou, Natacha Gonçalves-Sousa, Hiroshi Kubo, Marie Malissen, Venizelos Papayannopoulos, Karine Serre, Bruno Silva-Santos
Tumor-associated neutrophils suppress pro-tumoral IL-17+ γδ T cells through induction of oxidative stress
published pages: e2004990, ISSN: 1545-7885, DOI: 10.1371/journal.pbio.2004990
PLOS Biology 16/5 2020-01-24
2018 Nina Schmolka, Pedro H. Papotto, Paula Vargas Romero, Tiago Amado, Francisco J. Enguita, Ana Amorim, Ana F. Rodrigues, Katrina E. Gordon, Ana S. Coroadinha, Mark Boldin, Karine Serre, Amy H. Buck, Anita Q. Gomes, Bruno Silva-Santos
MicroRNA-146a controls functional plasticity in γδ T cells by targeting NOD1
published pages: eaao1392, ISSN: 2470-9468, DOI: 10.1126/sciimmunol.aao1392
Science Immunology 3/23 2020-01-24
2018 Duncan R. McKenzie, Iain Comerford, Bruno Silva-Santos, Shaun R. McColl
The Emerging Complexity of γδT17 Cells
published pages: , ISSN: 1664-3224, DOI: 10.3389/fimmu.2018.00796
Frontiers in Immunology 9 2020-01-24
2018 Daniel P. Inácio, Tiago Amado, Bruno Silva-Santos, Anita Q. Gomes
Control of T cell effector functions by miRNAs
published pages: 63-73, ISSN: 0304-3835, DOI: 10.1016/j.canlet.2018.04.011
Cancer Letters 427 2020-01-24
2017 Miguel Muñoz-Ruiz, Nital Sumaria, Daniel J. Pennington, Bruno Silva-Santos
Thymic Determinants of γδ T Cell Differentiation
published pages: 336-344, ISSN: 1471-4906, DOI: 10.1016/j.it.2017.01.007
Trends in Immunology 38/5 2020-01-24
2017 Bruno Silva-Santos, Jessica Strid
γδ T cells get adaptive
published pages: 370-372, ISSN: 1529-2908, DOI: 10.1038/ni.3705
Nature Immunology 18/4 2020-01-24
2017 Pedro H Papotto, Julie C Ribot, Bruno Silva-Santos
IL-17+ γδ T cells as kick-starters of inflammation
published pages: 604-611, ISSN: 1529-2908, DOI: 10.1038/ni.3726
Nature Immunology 18/6 2020-01-24
2018 Pedro H. Papotto, Annika Reinhardt, Immo Prinz, Bruno Silva-Santos
Innately versatile: γδ17 T cells in inflammatory and autoimmune diseases
published pages: 26-37, ISSN: 0896-8411, DOI: 10.1016/j.jaut.2017.11.006
Journal of Autoimmunity 87 2020-01-24
2017 Nital Sumaria, Capucine L. Grandjean, Bruno Silva-Santos, Daniel J. Pennington
Strong TCRγδ Signaling Prohibits Thymic Development of IL-17A-Secreting γδ T Cells
published pages: 2469-2476, ISSN: 2211-1247, DOI: 10.1016/j.celrep.2017.05.071
Cell Reports 19/12 2020-01-24
2017 Hiroshi Kubo, Sofia Mensurado, Natacha Gonçalves-Sousa, Karine Serre, Bruno Silva-Santos
Primary Tumors Limit Metastasis Formation through Induction of IL15-Mediated Cross-Talk between Patrolling Monocytes and NK Cells
published pages: 812-820, ISSN: 2326-6066, DOI: 10.1158/2326-6066.CIR-17-0082
Cancer Immunology Research 5/9 2020-01-24
2017 Pedro H Papotto, Natacha Gonçalves‐Sousa, Nina Schmolka, Andrea Iseppon, Sofia Mensurado, Brigitta Stockinger, Julie C Ribot, Bruno Silva‐Santos
IL‐23 drives differentiation of peripheral γδ17 T cells from adult bone marrow‐derived precursors
published pages: 1957-1967, ISSN: 1469-221X, DOI: 10.15252/embr.201744200
EMBO reports 18/11 2020-01-24
2016 Miguel Muñoz-Ruiz, Julie C Ribot, Ana R Grosso, Natacha Gonçalves-Sousa, Ana Pamplona, Daniel J Pennington, José R Regueiro, Edgar Fernández-Malavé, Bruno Silva-Santos
TCR signal strength controls thymic differentiation of discrete proinflammatory γδ T cell subsets
published pages: 721-727, ISSN: 1529-2908, DOI: 10.1038/ni.3424
Nature Immunology 17/6 2020-01-24
2016 S T Ribeiro, M Tesio, J C Ribot, E Macintyre, J T Barata, B Silva-Santos
Casein kinase 2 controls the survival of normal thymic and leukemic γδ T cells via promotion of AKT signaling
published pages: , ISSN: 0887-6924, DOI: 10.1038/leu.2016.363
Leukemia 2020-01-24

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