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
EMBL-European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SD, UK; MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge Biomedical Campus, Cambridge CB2 OQH, UK; Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK.
EMBL-European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SD, UK.
Cell Rep. 2014 May 22;7(4):1130-42. doi: 10.1016/j.celrep.2014.04.011. Epub 2014 May 10.
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.
辅助性T细胞2（Th2细胞）通过分泌多种细胞因子来调节蠕虫感染、过敏性疾病、肿瘤免疫和妊娠。很可能存在尚未被发现的Th2信号分子。尽管类固醇是已知的免疫调节剂，但免疫细胞从头合成类固醇的情况此前尚未得到描述。在此，我们证明了在蠕虫感染模型中，Th2细胞在体外和体内均可产生类固醇孕烯醇酮。单细胞RNA测序和定量PCR分析表明，Th2细胞中的孕烯醇酮合成与免疫抑制有关。作为对此的支持，我们表明孕烯醇酮可抑制Th细胞增殖和B细胞免疫球蛋白类别转换。我们还表明，产生类固醇的Th2细胞以Cyp11a1酶依赖性方式抑制Th细胞增殖。我们提出孕烯醇酮是一种“淋巴细胞类固醇”，即由淋巴细胞产生的类固醇。我们推测这种从头合成类固醇的现象可能是Th2介导的免疫反应的一种内在现象，以积极恢复免疫稳态。
