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Título: | Specific transcriptional programs differentiate ICOS from CD28 costimulatory signaling in human Naïve CD4+ T cells |
Autor: | Gigliotti, Casimiro Luca; Boggio, Elena; Favero, Francesco; Incarnato, Danny; Santoro, Carlo; Oliviero, Salvatore; Rojo, José María CSIC ORCID CVN ; Zucchelli, Silvia; Persichetti, Francesca; Baldanzi, Gianluca; Dianzani, Umberto; Corá, Davide | Fecha de publicación: | 5-sep-2022 | Editor: | Frontiers Media | Citación: | Frontiers in Immunology 13: 915963 (2022) | Resumen: | 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. | Descripción: | 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. | Versión del editor: | https://doi.org/10.3389/fimmu.2022.915963 | URI: | http://hdl.handle.net/10261/280405 | DOI: | 10.3389/fimmu.2022.915963 | ISSN: | 1664-3224 |
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