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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...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9484324/ https://www.ncbi.nlm.nih.gov/pubmed/36131938 http://dx.doi.org/10.3389/fimmu.2022.915963 |
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author | Gigliotti, Casimiro Luca Boggio, Elena Favero, Francesco Incarnato, Danny Santoro, Claudio Oliviero, Salvatore Rojo, Josè Maria Zucchelli, Silvia Persichetti, Francesca Baldanzi, Gianluca Dianzani, Umberto Corà, Davide |
author_facet | Gigliotti, Casimiro Luca Boggio, Elena Favero, Francesco Incarnato, Danny Santoro, Claudio Oliviero, Salvatore Rojo, Josè Maria Zucchelli, Silvia Persichetti, Francesca Baldanzi, Gianluca Dianzani, Umberto Corà, Davide |
author_sort | Gigliotti, Casimiro Luca |
collection | PubMed |
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. |
format | Online Article Text |
id | pubmed-9484324 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-94843242022-09-20 Specific transcriptional programs differentiate ICOS from CD28 costimulatory signaling in human Naïve CD4(+) T cells Gigliotti, Casimiro Luca Boggio, Elena Favero, Francesco Incarnato, Danny Santoro, Claudio Oliviero, Salvatore Rojo, Josè Maria Zucchelli, Silvia Persichetti, Francesca Baldanzi, Gianluca Dianzani, Umberto Corà, Davide Front Immunol Immunology 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. Frontiers Media S.A. 2022-09-05 /pmc/articles/PMC9484324/ /pubmed/36131938 http://dx.doi.org/10.3389/fimmu.2022.915963 Text en Copyright © 2022 Gigliotti, Boggio, Favero, Incarnato, Santoro, Oliviero, Rojo, Zucchelli, Persichetti, Baldanzi, Dianzani and Corà https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Immunology Gigliotti, Casimiro Luca Boggio, Elena Favero, Francesco Incarnato, Danny Santoro, Claudio Oliviero, Salvatore Rojo, Josè Maria Zucchelli, Silvia Persichetti, Francesca Baldanzi, Gianluca Dianzani, Umberto Corà, Davide Specific transcriptional programs differentiate ICOS from CD28 costimulatory signaling in human Naïve CD4(+) T cells |
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 naïve cd4(+) t cells |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9484324/ https://www.ncbi.nlm.nih.gov/pubmed/36131938 http://dx.doi.org/10.3389/fimmu.2022.915963 |
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