Single-cell RNA sequencing reveals T helper cells synthesizing steroids de novo to contribute to immune homeostasis.
Single-cell RNA sequencing reveals T helper cells synthesizing steroids de novo to contribute to immune homeostasis.
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单细胞RNA测序揭示了T辅助细胞合成从头开始的类固醇，从而有助于免疫稳态。
DOI：
10.1016/j.celrep.2014.04.011
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发表时间：
2014-05-22
期刊：
影响因子：
8.8
通讯作者：
Teichmann SA
中科院分区：
文献类型：
--
作者：
Mahata B;Zhang X;Kolodziejczyk AA;Proserpio V;Haim-Vilmovsky L;Taylor AE;Hebenstreit D;Dingler FA;Moignard V;Göttgens B;Arlt W;McKenzie AN;Teichmann SA
T助手2（TH2）细胞通过分泌各种细胞因子来调节蠕虫感染，过敏性疾病，肿瘤免疫力和妊娠。以前没有在这里表征。为此，我们表明Thementolone抑制了TH细胞的增殖和B细胞免疫球蛋白类别。淋巴细胞产生的类固醇。
Th2分化过程中立体生物合成途径的差异上调
辅助细胞在体外和体内产生类固醇untyolone
类固醇生成Th2细胞以CYP11A1依赖性方式抑制TH细胞增殖
妊娠烯醇抑制B细胞免疫球蛋白类别在体外切换
免疫细胞通过细胞因子和直接的细胞接触来表达，尽管已知免疫调节剂，但在这里，免疫细胞通常被认为是类固醇。体外和体内的类固醇孕妇抑制TH细胞增殖和B细胞免疫球蛋白类切换，类固醇生成的TH细胞抑制了TH细胞的增殖。
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. Differential upregulation of the steroid biosynthetic pathway during Th2 differentiation T helper cells produce the steroid pregnenolone in vitro and in vivo Steroidogenic Th2 cells suppress Th cell proliferation in a Cyp11a1-dependent manner Pregnenolone inhibits B cell immunoglobulin class switching in vitro Immune cells signal by secreting cytokines and by direct cell-to-cell contact. Although steroids are known to be immunoregulators, immune cells are not generally thought to be steroidogenic. Here, Mahata et al. demonstrate that T helper (Th) cells synthesize and secrete the steroid pregnenolone in vitro and in vivo. Pregnenolone inhibits Th cell proliferation and B cell immunoglobulin class switching, and steroidogenic Th cells inhibit Th cell proliferation. This evidence suggests that steroidogenic Th cells contribute to immune homeostasis.
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影响因子：
8
作者：
Angus, S. P.;Nevins, J. R.
通讯作者：
Nevins, J. R.
影响因子：
4.8
作者：
Carey, Kirstyn T.;Tan, Kheng H.;Cole, Timothy J.
通讯作者：
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影响因子：
82.9
作者：
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通讯作者：
Roncarolo, Maria-Grazia
影响因子：
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作者：
Camberis, Mali;Le Gros, Graham;Urban, Joseph Jr
通讯作者：
Urban, Joseph Jr
DOI：
10.1007/978-1-61737-979-6_2
发表时间：
2011
期刊：
Methods in molecular biology (Clifton, N.J.)
影响因子：
--
作者：
Collison, Lauren W;Vignali, Dario A A
通讯作者：
Vignali, Dario A A