FAM83H 调节产后T细胞的发育,通过胸膜组织组织
Betul Melike Ogan1,2, Veronika Forstlova3, Laura Jane Dowling3
1Laboratory of Transgenic Models of Diseases, Institute of Molecular Genetics of the Czech Academy of Sciences, Vestec, Czech Republic.
FAM83H蛋白对上皮细胞功能和免疫系统发育至关重要. 在小鼠中缺乏它会损害胸膜上皮细胞的成熟,导致T细胞的产生减少和发育缺陷.
科学领域:
- 分子和细胞生物学分子和细胞生物学
- 免疫学 免疫学 免疫学
- 发展生物学 发展生物学
背景情况:
- 序列相似性83H家族 (FAM83H) 是一种与甲状腺细胞蛋白相互作用的甲状腺细胞蛋白,与甲状腺素激酶1 (CK1) 和角质蛋白相互作用.
- FAM83H突变会导致非完美的乳腺发育,这表明它在质形成中的重要性.
- FAM83H调节细胞骨组织,细胞增殖和囊泡贩运.
研究的目的:
- 研究FAM83H在小鼠发育和免疫细胞生成中的作用.
- 描述Fam83h缺乏的小鼠及其胸膜表型.
- 探索FAM83H在胸膜上皮细胞中的功能背后的分子机制.
主要方法:
- 产生Fam83h缺乏的小鼠 (Fam83h-/-) 和被删除的CK1结合域的小鼠 (Fam83h∆87/∆87).
- 生成的小鼠模型的表型分析,包括生命力,外套,皮肤和活动.
- 评估淋巴细胞的发育,特别是胸腺中T细胞的发育.
- 胸膜上皮细胞 (TECs) 的单细胞转录组分析.
主要成果:
- 缺乏Fam83h的小鼠表现出低活力,体型较小,毛发粗,皮肤,软弱和低活性.
- 缺少Fam83h会导致淋巴细胞发育受损,特别是阻断T细胞扩张在胸腺的双阴性阶段3 (DN3).
- Fam83h在胸膜上皮细胞 (TECs) 中表达,其缺乏会破坏胸膜结构并减少T细胞输出.
- 单细胞转录组学揭示了Foxn1主调节器及其点在Fam83h-/-小鼠皮质TEC (cTEC) 中的减少表达.
结论:
- FAM83H对于正常发育,免疫细胞的产生和胸膜上皮细胞的成熟至关重要.
- FAM83H,可能与CK1结合,在调节TEC功能和胸膜架构方面发挥着关键作用.
- 这些发现突出了FAM83H作为T细胞发育的关键调节者,通过其对TEC的影响.
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