Specific transcriptional programs differentiate ICOS from CD28 costimulatory signaling in human Naïve CD4+ T cells
| Autor: | Casimiro Luca Gigliotti, Elena Boggio, Francesco Favero, Danny Incarnato, Claudio Santoro, Salvatore Oliviero, Josè Maria Rojo, Silvia Zucchelli, Francesca Persichetti, Gianluca Baldanzi, Umberto Dianzani, Davide Corà |
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| Přispěvatelé: | Fondazione Cariplo, Associazione Italiana per la Ricerca sul Cancro, Ministero dell'Istruzione, dell'Università e della Ricerca, Università degli Studi del Piemonte Orientale 'A. Avogadro', Fondazione Umberto Veronesi, Gigliotti, Casimiro Luca [0000-0002-3127-5686], Boggio, Elena [0000-0003-2700-3597], Incarnato, Danny [0000-0003-3944-2327], Oliviero, Salvatore [0000-0002-3405-765X], Rojo, José María [0000-0001-9032-0072], Zucchelli, Silvia [0000-0003-4556-2990], Persichetti, Francesca [0000-0002-9804-644X], Baldanzi, Gianluca [0000-0002-1370-9903], Dianzani, Umberto [0000-0001-6723-3931], Corá, Davide [0000-0003-4123-1705], Gigliotti, Casimiro Luca, Boggio, Elena, Incarnato, Danny, Oliviero, Salvatore, Rojo, José María, Zucchelli, Silvia, Persichetti, Francesca, Baldanzi, Gianluca, Dianzani, Umberto, Corá, Davide, Molecular Genetics |
| Rok vydání: | 2022 |
| Předmět: |
CD4-Positive T-Lymphocytes
p38 Mitogen-Activated Protein Kinases/metabolism Transcription Genetic Immunology Receptors Antigen T-Cell Receptors Antigen T-Cell/metabolism p38 Mitogen-Activated Protein Kinases Inducible T-Cell Co-Stimulator Protein Cholesterol/metabolism Cholesterol T-Cell/metabolism CD28 Antigens Antigen Inducible T-Cell Co-Stimulator Protein/metabolism Receptors Immunology and Allergy Humans Glycosaminoglycans/metabolism Glycosaminoglycans |
| Zdroj: | Digital.CSIC. Repositorio Institucional del CSIC instname Frontiers in Immunology, 13:915963. Frontiers Media SA |
| ISSN: | 1664-3224 |
| Popis: | 14 p.-5 fig. This work is dedicated to the memory of our colleague SZ. SZ was an extraordinary person, a great friend, a remarkable scholar and an unfailing mentor for our students. Her passion for life and research will always be an example. We miss her a lot. Costimulatory molecules of the CD28 family play a crucial role in the activation of immune responses in T lymphocytes, complementing and modulating signals originating from the T-cell receptor (TCR) complex. Although distinct functional roles have been demonstrated for each family member, the specific signaling pathways differentiating ICOS- from CD28-mediated costimulation during early T-cell activation are poorly characterized. In the present study, we have performed RNA-Seq-based global transcriptome profiling of anti-CD3-treated naïve CD4+ T cells upon costimulation through either inducible costimulator (ICOS) or CD28, revealing a set of signaling pathways specifically associated with each signal. In particular, we show that CD3/ICOS costimulation plays a major role in pathways related to STAT3 function and osteoarthritis (OA), whereas the CD3/CD28 axis mainly regulates p38 MAPK signaling. Furthermore, we report the activation of distinct immunometabolic pathways, with CD3/ICOS costimulation preferentially targeting glycosaminoglycans (GAGs) and CD3/CD28 regulating mitochondrial respiratory chain and cholesterol biosynthesis. These data suggest that ICOS and CD28 costimulatory signals play distinct roles during the activation of naïve T cells by modulating distinct sets of immunological and immunometabolic genes. This work was supported by Fondazione CARIPLO (2014-0812) to SZ. and by the Associazione Italiana Ricerca sul Cancro (IG 20714 to UD and IG 20240 to SO, AIRC, Milano), and Fondazione Cariplo (2017-0535) to UD. DC acknowledge support by the Italian Ministry of University and Research program “Departments of Excellence 2018-2022”, AGING Project – Department of Translational Medicine, Università del Piemonte Orientale. Fondazione Umberto Veronesi, Milan, Italy supported EB. |
| Databáze: | OpenAIRE |
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