Department of Developmental Immunology, Max Planck Institute of Immunobiology and Epigenetics, Freiburg, Germany.
Center for Bioscience Research and Education, Utsunomiya University, Utsunomiya, Tochigi, 321-8505, Japan.
Nat Commun. 2023 Jun 20;14(1):3645. doi: 10.1038/s41467-023-39422-4.
Unconventional T cells, such as innate natural killer T cells (iNKT) cells, are an important part of vertebrate immune defences. iNKT recognise glycolipids through a T cell receptor (TCR) that is composed of a semi-invariant TCR α chain, paired with a restricted set of TCR β chains. Here, we show that splicing of the cognate Trav11-Traj18-Trac pre-mRNA encoding the characteristic Vα14Jα18 variable region of this semi-invariant TCR depends on the presence of Tnpo3. The Tnpo3 gene encodes a nuclear transporter of the β-karyopherin family whose cargo includes various splice regulators. The block of iNKT cell development in the absence of Tnpo3 can be overcome by transgenic provision of a rearranged Trav11-Traj18-Trac cDNA, indicating that Tnpo3 deficiency does not interfere with the development of iNKT cells per se. Our study thus identifies a role for Tnpo3 in regulating the splicing of the pre-mRNA encoding the cognate TCRα chain of iNKT cells.
非传统 T 细胞，如先天自然杀伤 T 细胞（iNKT）细胞，是脊椎动物免疫防御的重要组成部分。iNKT 通过由半不变 TCRα 链与一组受限的 TCRβ 链组成的 T 细胞受体（TCR）识别糖脂。在这里，我们表明编码该半不变 TCR 特征性 Vα14Jα18 可变区的同源 Trav11-Traj18-Trac 前体 mRNA 的剪接依赖于 Tnpo3 的存在。Tnpo3 基因编码 β-核孔蛋白家族的核转运蛋白，其货物包括各种剪接调节剂。在缺乏 Tnpo3 的情况下，iNKT 细胞发育受阻可以通过转基因提供重排的 Trav11-Traj18-Trac cDNA 来克服，这表明 Tnpo3 缺乏本身并不干扰 iNKT 细胞的发育。因此，我们的研究确定了 Tnpo3 在调节 iNKT 细胞的同源 TCRα 链前体 mRNA 剪接中的作用。
