近日，加拿大大学教授Tak W. Mak及其研究组揭示了胸腺细胞阴性选择的胆碱能调控。这一研究成果于2025年5月21日发表在国际顶尖学术期刊《自然—免疫学》上。

研究人员发现，motheme CD4⁺CD8⁺双阳性胸腺细胞表达高水平的α9烟碱AChR (nAChR)，该受体控制胸腺阴性选择。α9 nAChR缺陷小鼠显示T细胞受体（TCR）库和CD4⁺和CD8⁺ T混合骨髓嵌合体环境中的细胞。α9 nAChR介导的信号调节TCR强度和胸腺细胞存活。胸腺簇状细胞，B细胞和一些T细胞表达胆碱乙酰转移酶，是潜在的乙酰胆碱受体，乙酰胆碱来源于T细胞，起着最重要的作用。

此外，胸腺细胞发育过程中α9 nAChR缺失有助于小鼠自身免疫性疾病的发生。他们的研究结果揭示了一种控制免疫细胞发育的机制，该机制涉及胆碱能信号传导。

据了解，免疫系统和神经系统使用一种共同的化学语言进行交流，即涉及乙酰胆碱（ACh）及其受体（AChRs）的胆碱能信号。这种语言是否以及如何调节免疫系统的发育尚不清楚。

附：英文原文

Title: Cholinergic regulation of thymocyte negative selection

Author: Liu, Shaofeng, Zheng, Chunxing, Nechanitzky, Robert, Luo, Ping, Ramachandran, Parameswaran, Nguyen, Dat, Elia, Andrew J., Moghadas Jafari, Soode, Law, Rhoda, Snow, Bryan E., Wakeham, Andrew C., Berger, Thorsten, Chen, Hui, Gill, Kyle T., Mcwilliam, Ryan, Fortin, Jerome, Modares, Nastaran Fazel, Saunders, Mary E., Murakami, Kiichi, Qiu, Yangmin, You, Zhiwei, Mohtashami, Mahmood, Qi, Hai, Ohashi, Pamela S., Ziga-Pflcker, Juan Carlos, Mak, Tak W.

Issue&Volume: 2025-05-21

Abstract: The immune and nervous systems use a common chemical language for communication, namely, the cholinergic signaling involving acetylcholine (ACh) and its receptors (AChRs). Whether and how this language also regulates the development of the immune system is poorly understood. Here, we show that mouse CD4+CD8+ double-positive thymocytes express high levels of α9 nicotinic AChR (nAChR) and that this receptor controls thymic negative selection. α9 nAChR-deficient mice show an altered Tcell receptor (TCR) repertoire and reduced CD4+ and CD8+ Tcells in a mixed bone marrow chimera setting. α9 nAChR-mediated signaling regulates TCR strength and thymocyte survival. Thymic tuft cells, Bcells and some Tcells express choline acetyltransferase and are potential ACh sources, with ACh derived from Tcells having the most important role. Furthermore, α9 nAChR deficiency during thymocyte development contributes to the altered development of autoimmune diseases in mice. Our results thus reveal a mechanism controlling immune cell development that involves cholinergic signaling.

DOI: 10.1038/s41590-025-02152-4

Source: https://www.nature.com/articles/s41590-025-02152-4