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Single-cell RNA sequencing reveals T helper cells synthesizing steroids de novo to contribute to immune homeostasis
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Mahata, Bidesh, Zhang, Xiuwei, Kolodziejczyk, Aleksandra A., Proserpio, Valentina, Haim-Vilmovsky, Liora, Taylor, Angela E., Hebenstreit, Daniel, Dingler, Felix A., Moignard, Victoria, Göttgens, Berthold, Arlt, Wiebke, McKenzie, Andrew N. J. and Teichmann, Sarah A. (2014) Single-cell RNA sequencing reveals T helper cells synthesizing steroids de novo to contribute to immune homeostasis. Cell Reports, Volume 7 (Number 4). pp. 1130-1142. doi:10.1016/j.celrep.2014.04.011 ISSN 2211-1247.
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Official URL: http://dx.doi.org/10.1016/j.celrep.2014.04.011
Abstract
T helper 2 (Th2) cells regulate helminth infections, allergic disorders, tumor immunity, and pregnancy by secreting various cytokines. It is likely that there are undiscovered Th2 signaling molecules. Although steroids are known to be immunoregulators, de novo steroid production from immune cells has not been previously characterized. Here, we demonstrate production of the steroid pregnenolone by Th2 cells in vitro and in vivo in a helminth infection model. Single-cell RNA sequencing and quantitative PCR analysis suggest that pregnenolone synthesis in Th2 cells is related to immunosuppression. In support of this, we show that pregnenolone inhibits Th cell proliferation and B cell immunoglobulin class switching. We also show that steroidogenic Th2 cells inhibit Th cell proliferation in a Cyp11a1 enzyme-dependent manner. We propose pregnenolone as a “lymphosteroid,” a steroid produced by lymphocytes. We speculate that this de novo steroid production may be an intrinsic phenomenon of Th2-mediated immune responses to actively restore immune homeostasis.
| Item Type: | Journal Article | ||||||||||
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| Subjects: | Q Science > QP Physiology | ||||||||||
| Divisions: | Faculty of Science, Engineering and Medicine > Science > Life Sciences (2010- ) | ||||||||||
| Library of Congress Subject Headings (LCSH): | Th2 cells, Pregnenolone -- Synthesis, Helminthiasis | ||||||||||
| Journal or Publication Title: | Cell Reports | ||||||||||
| Publisher: | Elsevier Inc. | ||||||||||
| ISSN: | 2211-1247 | ||||||||||
| Official Date: | 22 May 2014 | ||||||||||
| Dates: |
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| Volume: | Volume 7 | ||||||||||
| Number: | Number 4 | ||||||||||
| Page Range: | pp. 1130-1142 | ||||||||||
| DOI: | 10.1016/j.celrep.2014.04.011 | ||||||||||
| Status: | Peer Reviewed | ||||||||||
| Publication Status: | Published | ||||||||||
| Access rights to Published version: | Open Access (Creative Commons) | ||||||||||
| Date of first compliant deposit: | 27 December 2015 | ||||||||||
| Date of first compliant Open Access: | 27 December 2015 | ||||||||||
| Funder: | Lister Institute of Preventive Medicine, European Research Council (ERC), Medical Research Council (Great Britain) (MRC), European Bioinformatics Institute (EMBL-EBI), Wellcome Trust (London, England), Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung [Swiss National Science Foundation] (SNSF) | ||||||||||
| Grant number: | 260507 (ERC), PBELP2_143538 (SNSF) |
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