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糖酵解通过调节FOXP3外显子2剪接变体的表达来控制人类调节性T细胞的诱导。

Glycolysis controls the induction of human regulatory T cells by modulating the expression of FOXP3 exon 2 splicing variants.

作者信息

De Rosa Veronica, Galgani Mario, Porcellini Antonio, Colamatteo Alessandra, Santopaolo Marianna, Zuchegna Candida, Romano Antonella, De Simone Salvatore, Procaccini Claudio, La Rocca Claudia, Carrieri Pietro Biagio, Maniscalco Giorgia Teresa, Salvetti Marco, Buscarinu Maria Chiara, Franzese Adriana, Mozzillo Enza, La Cava Antonio, Matarese Giuseppe

机构信息

Laboratorio di Immunologia, Istituto di Endocrinologia e Oncologia Sperimentale, Consiglio Nazionale delle Ricerche, Napoli, Italy.

Unità di NeuroImmunologia, Fondazione Santa Lucia, Roma, Italy.

出版信息

Nat Immunol. 2015 Nov;16(11):1174-84. doi: 10.1038/ni.3269. Epub 2015 Sep 28.

DOI:10.1038/ni.3269
PMID:26414764
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4868085/
Abstract

Human regulatory T cells (T(reg) cells) that develop from conventional T cells (T(conv) cells) following suboptimal stimulation via the T cell antigen receptor (TCR) (induced T(reg) cells (iT(reg) cells)) express the transcription factor Foxp3, are suppressive, and display an active proliferative and metabolic state. Here we found that the induction and suppressive function of iT(reg) cells tightly depended on glycolysis, which controlled Foxp3 splicing variants containing exon 2 (Foxp3-E2) through the glycolytic enzyme enolase-1. The Foxp3-E2-related suppressive activity of iT(reg) cells was altered in human autoimmune diseases, including multiple sclerosis and type 1 diabetes, and was associated with impaired glycolysis and signaling via interleukin 2. This link between glycolysis and Foxp3-E2 variants via enolase-1 shows a previously unknown mechanism for controlling the induction and function of T(reg) cells in health and in autoimmunity.

摘要

人类调节性T细胞（T(reg)细胞）由常规T细胞（T(conv)细胞）经T细胞抗原受体（TCR）次优刺激后发育而来（诱导性T(reg)细胞（iT(reg)细胞）），表达转录因子Foxp3，具有抑制作用，并呈现活跃的增殖和代谢状态。我们发现，iT(reg)细胞的诱导和抑制功能紧密依赖糖酵解，糖酵解通过糖酵解酶烯醇化酶-1控制含第2外显子的Foxp3剪接变体（Foxp3-E2）。iT(reg)细胞的Foxp3-E2相关抑制活性在包括多发性硬化症和1型糖尿病在内的人类自身免疫性疾病中发生改变，且与糖酵解受损及白细胞介素2信号传导受损有关。通过烯醇化酶-1实现的糖酵解与Foxp3-E2变体之间的这种联系揭示了一种此前未知的机制，该机制可在健康和自身免疫状态下控制T(reg)细胞的诱导和功能。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/468d/4868085/faa90c07250a/nihms783044f8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/468d/4868085/2e067335234d/nihms783044f1.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/468d/4868085/a254d4dcc647/nihms783044f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/468d/4868085/a1f3646c99d6/nihms783044f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/468d/4868085/6214939553bb/nihms783044f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/468d/4868085/65fae5237cba/nihms783044f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/468d/4868085/a8f0d4ae2c3b/nihms783044f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/468d/4868085/faa90c07250a/nihms783044f8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/468d/4868085/2e067335234d/nihms783044f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/468d/4868085/b31dd05c0902/nihms783044f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/468d/4868085/a254d4dcc647/nihms783044f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/468d/4868085/a1f3646c99d6/nihms783044f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/468d/4868085/6214939553bb/nihms783044f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/468d/4868085/65fae5237cba/nihms783044f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/468d/4868085/a8f0d4ae2c3b/nihms783044f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/468d/4868085/faa90c07250a/nihms783044f8.jpg

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