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Image_1_Specific transcriptional programs differentiate ICOS from CD28 costimulatory signaling in human Naïve CD4+ T cells.jpeg (288.13 kB)

Image_1_Specific transcriptional programs differentiate ICOS from CD28 costimulatory signaling in human Naïve CD4+ T cells.jpeg

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posted on 2022-09-05, 14:00 authored by 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

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.

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