[en] Pregnenolone sulfate is a steroid metabolite of the steroidogenesis precursor, pregnenolone, with similar functional properties, including immunosuppression. We recently reported an elevation in serum levels of pregnenolone sulfate in children with malaria, contributing to an immunosuppressed state. Yet, the molecular mechanisms in which this steroid exerts its immunoregulatory functions are lacking. In this study, we examined the effects of pregnenolone sulfate on T cell viability, proliferation and transcriptome. We observed a pregnenolone sulfate dose-dependent induction of T cell death and reduction in proliferation. RNA sequencing analysis of pregnenolone sulfate-treated T cells for 2 and 24 h revealed the downregulation of pro-inflammatory genes and the upregulation of the steroid nuclear receptor superfamily, NR4A, as early-response genes. We also report a strong activation of the integrated stress response mediated by the upregulation of EIF2AK3. These results contribute to the knowledge on transcriptional regulation driving the immunoregulatory effects of pregnenolone sulfate on T cells.
Disciplines :
Genetics & genetic processes
Author, co-author :
El Hajj, Yasmine; Program in Biology, Division of Science and Mathematics, New York University Abu Dhabi, Abu Dhabi, United Arab Emirates
Shahin, Tala; Program in Biology, Division of Science and Mathematics, New York University Abu Dhabi, Abu Dhabi, United Arab Emirates
Dieng, Mame Massar ; Université de Liège - ULiège > TERRA Research Centre ; Program in Biology, Division of Science and Mathematics, New York University Abu Dhabi, Abu Dhabi, United Arab Emirates
Alshaikh, Manar; Program in Biology, Division of Science and Mathematics, New York University Abu Dhabi, Abu Dhabi, United Arab Emirates
Khair, Mostafa; Core Technology Platforms, New York University Abu Dhabi, Abu Dhabi, United Arab Emirates
Manikandan, Vinu; Program in Biology, Division of Science and Mathematics, New York University Abu Dhabi, Abu Dhabi, United Arab Emirates
Idaghdour, Youssef; Program in Biology, Division of Science and Mathematics, New York University Abu Dhabi, Abu Dhabi, United Arab Emirates. youssef.idaghdour@nyu.edu
Language :
English
Title :
Pregnenolone sulfate induces transcriptional and immunoregulatory effects on T cells.
We thank the Center for Genomics and Systems Biology, NYUAD Core Bioinformatics and Technology Platforms (K. Gunsalus, N. Drou, M. Arnoux and M. Sultana). This work was funded by NYUAD grant ADHPG AD105 to Y.I.
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