Single-cell RNA sequencing reveals T helper cells synthesizing steroids de novo to contribute to immune homeostasis.
IF: 9.995
Cited by: 149


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.



MeSH terms

Mice, Inbred C57BL
Sequence Analysis, RNA
Single-Cell Analysis
Th1 Cells
Th2 Cells


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

Recommend literature

Similar data