Tespa1,全称Thymocyte-expressed, Positive Selection-associated 1,是一种在胸腺细胞中表达的蛋白质,它在胸腺细胞的选择和成熟过程中起着重要作用。Tespa1属于胸腺细胞发育和T细胞受体(TCR)信号传导的关键信号分子,其功能与胸腺细胞对低亲和力自身肽-MHC配体的反应密切相关。胸腺细胞必须对这些配体有较高的敏感性,以便在成熟为CD4+和CD8+ T细胞之前,能够对它们做出反应。Tespa1在胸腺细胞中通过与IP3R(Inositol 1,4,5-trisphosphate receptor)相互作用,促进钙信号传导和随后的MAPK激活,从而调节TCR介导的信号传导[4]。
在多种疾病中,Tespa1的表达和功能与疾病的易感性和进展相关。例如,在卵巢癌中,Tespa1的表达水平与疾病的进展相关。一项研究发现,在卵巢癌患者中,Tespa1的表达水平显著升高,且Tespa1的表达水平与患者的预后相关[1]。此外,Tespa1的表达水平还与哮喘的发病机制相关。在哮喘患者中,Tespa1的表达水平显著降低,且Tespa1的表达水平与患者的病情严重程度相关[2]。此外,Tespa1的表达水平还与类风湿性关节炎(RA)的易感性相关。在RA患者中,Tespa1的表达水平显著降低,且Tespa1的表达水平与患者的疾病活动度相关[3]。此外,Tespa1的表达水平还与强直性脊柱炎(AS)的病情严重程度相关。在AS患者中,Tespa1的表达水平与患者的疼痛程度和疾病活动度相关[5]。
综上所述,Tespa1是一种在胸腺细胞发育和TCR信号传导中起着重要作用的蛋白质。Tespa1的表达和功能与多种疾病的易感性和进展相关,包括卵巢癌、哮喘、RA和AS。因此,研究Tespa1在疾病中的作用机制对于理解疾病的发病机制和开发新的治疗方法具有重要意义。
参考文献:
1. Dondi, Arthur, Lischetti, Ulrike, Jacob, Francis, Beisel, Christian, Beerenwinkel, Niko. 2023. Detection of isoforms and genomic alterations by high-throughput full-length single-cell RNA sequencing in ovarian cancer. In Nature communications, 14, 7780. doi:10.1038/s41467-023-43387-9. https://pubmed.ncbi.nlm.nih.gov/38012143/
2. Yang, Ruhui, Wang, Guangli, Li, Lingyun, Lu, Linrong, Wu, Songquan. 2020. Tespa1 plays a role in the modulation of airway hyperreactivity through the IL-4/STAT6 pathway. In Journal of translational medicine, 18, 444. doi:10.1186/s12967-020-02621-4. https://pubmed.ncbi.nlm.nih.gov/33228696/
3. Yao, Yunliang, Zhang, Hui, Shao, Shengwen, Zhang, Ting, Sun, Hui. 2015. Tespa1 is associated with susceptibility but not severity of rheumatoid arthritis in the Zhejiang Han population in China. In Clinical rheumatology, 34, 665-71. doi:10.1007/s10067-015-2900-7. https://pubmed.ncbi.nlm.nih.gov/25736038/
4. Liang, Jingjing, Lyu, Jun, Zhao, Meng, Liu, Wanli, Lu, Linrong. 2017. Tespa1 regulates T cell receptor-induced calcium signals by recruiting inositol 1,4,5-trisphosphate receptors. In Nature communications, 8, 15732. doi:10.1038/ncomms15732. https://pubmed.ncbi.nlm.nih.gov/28598420/
5. Liu, Si, Liu, Li, Wu, Shanshan, Wang, Li, Xin, Lihong. . Lack of association between TESPA1 gene polymorphisms (rs1801876, rs2171497, rs4758994, and rs997173) and ankylosing spondylitis in a Chinese population. In Inflammation, 37, 2040-6. doi:10.1007/s10753-014-9936-8. https://pubmed.ncbi.nlm.nih.gov/24893580/