Single-cell RNA sequencing reveals T helper cells synthesizing steroids de novo to contribute to immune homeostasis
File(s)
Published version
Author(s)
Mahata, Bidesh
Zhang, Xiuwei
Kolodziejczyk, Aleksandra A
Proserpio, Valentina
Haim-Vilmovsky, Liora
Type
Journal Article
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.
Date Issued
2014-05-22
Date Acceptance
2014-04-03
Citation
Cell reports, 2014, 7 (4), pp.1130-1142
ISSN
2211-1247
Publisher
Elsevier
Start Page
1130
End Page
1142
Journal / Book Title
Cell reports
Volume
7
Issue
4
Copyright Statement
ª2014 The Authors This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/3.0/).
License URL
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/24813893
PII: S2211-1247(14)00298-8
Subjects
Cell Biology
GENES
GLUCOCORTICOID PRODUCTION
Life Sciences & Biomedicine
LUNG
MECHANISMS
MICE
NOISE
Science & Technology
SUPPRESSION
TH2 RESPONSES
TRANSCRIPTION
Publication Status
Published
Coverage Spatial
United States
Date Publish Online
2014-05-09