Specific transcriptional programs differentiate ICOS from CD28 costimulatory signaling in human Naïve CD4+ T cells
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 specif...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-09-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.915963/full |
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| author | Casimiro Luca Gigliotti Casimiro Luca Gigliotti Elena Boggio Elena Boggio Francesco Favero Francesco Favero Francesco Favero Danny Incarnato Claudio Santoro Claudio Santoro Claudio Santoro Salvatore Oliviero Salvatore Oliviero Josè Maria Rojo Silvia Zucchelli Silvia Zucchelli Silvia Zucchelli Francesca Persichetti Francesca Persichetti Gianluca Baldanzi Gianluca Baldanzi Gianluca Baldanzi Umberto Dianzani Umberto Dianzani Umberto Dianzani Davide Corà Davide Corà Davide Corà |
| author_facet | Casimiro Luca Gigliotti Casimiro Luca Gigliotti Elena Boggio Elena Boggio Francesco Favero Francesco Favero Francesco Favero Danny Incarnato Claudio Santoro Claudio Santoro Claudio Santoro Salvatore Oliviero Salvatore Oliviero Josè Maria Rojo Silvia Zucchelli Silvia Zucchelli Silvia Zucchelli Francesca Persichetti Francesca Persichetti Gianluca Baldanzi Gianluca Baldanzi Gianluca Baldanzi Umberto Dianzani Umberto Dianzani Umberto Dianzani Davide Corà Davide Corà Davide Corà |
| author_sort | Casimiro Luca Gigliotti |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-12T21:22:15Z |
| format | Article |
| id | doaj.art-55eb914dee7e467a8a6a4d3d915b6074 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-12T21:22:15Z |
| publishDate | 2022-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-55eb914dee7e467a8a6a4d3d915b60742022-12-22T03:16:16ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-09-011310.3389/fimmu.2022.915963915963Specific transcriptional programs differentiate ICOS from CD28 costimulatory signaling in human Naïve CD4+ T cellsCasimiro Luca Gigliotti0Casimiro Luca Gigliotti1Elena Boggio2Elena Boggio3Francesco Favero4Francesco Favero5Francesco Favero6Danny Incarnato7Claudio Santoro8Claudio Santoro9Claudio Santoro10Salvatore Oliviero11Salvatore Oliviero12Josè Maria Rojo13Silvia Zucchelli14Silvia Zucchelli15Silvia Zucchelli16Francesca Persichetti17Francesca Persichetti18Gianluca Baldanzi19Gianluca Baldanzi20Gianluca Baldanzi21Umberto Dianzani22Umberto Dianzani23Umberto Dianzani24Davide Corà25Davide Corà26Davide Corà27Department of Health Sciences, University of Piemonte Orientale, Novara, ItalyInterdisciplinary Research Center of Autoimmune Diseases (IRCAD), University of Piemonte Orientale, Novara, ItalyDepartment of Health Sciences, University of Piemonte Orientale, Novara, ItalyInterdisciplinary Research Center of Autoimmune Diseases (IRCAD), University of Piemonte Orientale, Novara, ItalyDepartment of Health Sciences, University of Piemonte Orientale, Novara, ItalyInterdisciplinary Research Center of Autoimmune Diseases (IRCAD), University of Piemonte Orientale, Novara, ItalyCAAD - Center for Translational Research on Autoimmune and Allergic Disease, Novara, ItalyDepartment of Molecular Genetics, Groningen Biomolecular Sciences and Biotechnology Institute (GBB), University of Groningen, Groningen, NetherlandsDepartment of Health Sciences, University of Piemonte Orientale, Novara, ItalyInterdisciplinary Research Center of Autoimmune Diseases (IRCAD), University of Piemonte Orientale, Novara, ItalyCAAD - Center for Translational Research on Autoimmune and Allergic Disease, Novara, ItalyDipartimento di Scienze della Vita e Biologia dei Sistemi, Università di Torino, Torino, ItalyItalian Institute for Genomic Medicine (IIGM), Torino, ItalyCentro de Investigaciones Biológicas Margarita Salas, Consejo Superior de Investigaciones Cientificas (CSIC), Madrid, SpainDepartment of Health Sciences, University of Piemonte Orientale, Novara, ItalyInterdisciplinary Research Center of Autoimmune Diseases (IRCAD), University of Piemonte Orientale, Novara, ItalyCAAD - Center for Translational Research on Autoimmune and Allergic Disease, Novara, ItalyDepartment of Health Sciences, University of Piemonte Orientale, Novara, ItalyInterdisciplinary Research Center of Autoimmune Diseases (IRCAD), University of Piemonte Orientale, Novara, ItalyInterdisciplinary Research Center of Autoimmune Diseases (IRCAD), University of Piemonte Orientale, Novara, ItalyCAAD - Center for Translational Research on Autoimmune and Allergic Disease, Novara, ItalyDepartment of Translational Medicine, University of Piemonte Orientale, Novara, ItalyDepartment of Health Sciences, University of Piemonte Orientale, Novara, ItalyInterdisciplinary Research Center of Autoimmune Diseases (IRCAD), University of Piemonte Orientale, Novara, ItalyBiochemical Chemistry, “Maggiore della Carità” University Hospital, Novara, ItalyInterdisciplinary Research Center of Autoimmune Diseases (IRCAD), University of Piemonte Orientale, Novara, ItalyCAAD - Center for Translational Research on Autoimmune and Allergic Disease, Novara, ItalyDepartment of Translational Medicine, University of Piemonte Orientale, Novara, ItalyCostimulatory 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.https://www.frontiersin.org/articles/10.3389/fimmu.2022.915963/fullhuman CD4+ T cellsT-cell receptorICOSCD28RNA sequencing |
| spellingShingle | Casimiro Luca Gigliotti Casimiro Luca Gigliotti Elena Boggio Elena Boggio Francesco Favero Francesco Favero Francesco Favero Danny Incarnato Claudio Santoro Claudio Santoro Claudio Santoro Salvatore Oliviero Salvatore Oliviero Josè Maria Rojo Silvia Zucchelli Silvia Zucchelli Silvia Zucchelli Francesca Persichetti Francesca Persichetti Gianluca Baldanzi Gianluca Baldanzi Gianluca Baldanzi Umberto Dianzani Umberto Dianzani Umberto Dianzani Davide Corà Davide Corà Davide Corà Specific transcriptional programs differentiate ICOS from CD28 costimulatory signaling in human Naïve CD4+ T cells Frontiers in Immunology human CD4+ T cells T-cell receptor ICOS CD28 RNA sequencing |
| title | Specific transcriptional programs differentiate ICOS from CD28 costimulatory signaling in human Naïve CD4+ T cells |
| title_full | Specific transcriptional programs differentiate ICOS from CD28 costimulatory signaling in human Naïve CD4+ T cells |
| title_fullStr | Specific transcriptional programs differentiate ICOS from CD28 costimulatory signaling in human Naïve CD4+ T cells |
| title_full_unstemmed | Specific transcriptional programs differentiate ICOS from CD28 costimulatory signaling in human Naïve CD4+ T cells |
| title_short | Specific transcriptional programs differentiate ICOS from CD28 costimulatory signaling in human Naïve CD4+ T cells |
| title_sort | specific transcriptional programs differentiate icos from cd28 costimulatory signaling in human naive cd4 t cells |
| topic | human CD4+ T cells T-cell receptor ICOS CD28 RNA sequencing |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.915963/full |
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