Single-cell RNA sequencing reveals T helper cells synthesizing steroids de novo to contribute to immune homeostasis.

IF: 9.995

Cited by: 149

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.

Keywords

PROCEDURE

MeSH terms

Animals

Homeostasis

Humans

Mice

Mice, Inbred C57BL

Pregnenolone

RNA

Sequence Analysis, RNA

Single-Cell Analysis

Th1 Cells

Th2 Cells

Transcriptome

Authors

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

Teichmann, Sarah A

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