Department of Immunology, The John Curtin School of Medical Research, The Australian National University, Canberra, Australia.
PLoS One. 2011;6(11):e26440. doi: 10.1371/journal.pone.0026440. Epub 2011 Nov 4.
Natural killer T (NKT) cells represent an important regulatory T cell subset that develops in the thymus and contains immature (NK1.1(lo)) and mature (NK1.1(hi)) cell subsets. Here we show in mice that an inherited mutation in heterogeneous ribonucleoprotein L-like protein (hnRNPLL(thunder)), that shortens the survival of conventional T cells, has no discernible effect on NKT cell development, homeostasis or effector function. Thus, Hnrpll deficiency effectively increases the NKT∶T cell ratio in the periphery. However, Hnrpll mutation disrupts CD45RA, RB and RC exon silencing of the Ptprc mRNA in both NKT and conventional T cells, and leads to a comparably dramatic shift to high molecular weight CD45 isoforms. In addition, Hnrpll mutation has a cell intrinsic effect on the expression of the developmentally regulated cell surface marker NK1.1 on NKT cells in the thymus and periphery but does not affect cell numbers. Therefore our results highlight both overlapping and divergent roles for hnRNPLL between conventional T cells and NKT cells. In both cell subsets it is required as a trans-acting factor to regulate alternative splicing of the Ptprc mRNA, but it is only required for survival of conventional T cells.
自然杀伤 T (NKT) 细胞是一种重要的调节性 T 细胞亚群，它在胸腺中发育，包含不成熟（NK1.1(lo)）和成熟（NK1.1(hi)）细胞亚群。在这里，我们在小鼠中表明，不均一核糖核蛋白 L 样蛋白 (hnRNPLL(thunder)) 的遗传突变缩短了常规 T 细胞的存活时间，但对 NKT 细胞的发育、稳态或效应功能没有明显影响。因此，Hnrpll 缺乏有效地增加了外周血中 NKT∶T 细胞的比例。然而，Hnrpll 突变破坏了 NKT 和常规 T 细胞中 Ptprc mRNA 的 CD45RA、RB 和 RC 外显子沉默，并导致 CD45 同种型向高分子量的显著转变。此外，Hnrpll 突变对 NKT 细胞在胸腺和外周血中发育调节的表面标记 NK1.1 的表达具有细胞内在的影响，但不影响细胞数量。因此，我们的结果强调了 hnRNPLL 在常规 T 细胞和 NKT 细胞之间既有重叠又有不同的作用。在这两个细胞亚群中，它都作为一种反式作用因子来调节 Ptprc mRNA 的选择性剪接，但它只对常规 T 细胞的存活是必需的。
