A point mutation in the linker domain of mouse STAT5A is associated with impaired NK-cell regulation.,Genes and Immunity

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A point mutation in the linker domain of mouse STAT5A is associated with impaired NK-cell regulation.
Genes and Immunity ( IF 5.0 ) Pub Date : 2019-10-08 , DOI: 10.1038/s41435-019-0088-6
Salma Chehboun _{1,

2} , Gabriel André Leiva-Torres _{1,

2} , Benoît Charbonneau _{1,

2} , Robert Eveleigh ₃ , Guillaume Bourque ₃ , Silvia Marina Vidal _{1,

2}

Affiliation

The transcription factor STAT5 is critical for peripheral NK-cell survival, proliferation, and cytotoxic function. STAT5 refers to two highly related proteins, STAT5A and STAT5B. In this study, we verified the importance of STAT5A isoform for NK cells. We characterized an incidental chemically induced W484G mutation in the Stat5a gene and found that this mutation was associated with a reduction of STAT5A protein expression. Closer examination of NK-cell subsets from Stat5a mutant mice showed marked reductions in NK-cell number and maturation. IL-15 treatment of Stat5a mutant NK cells exhibited defective induction of both STAT5 and mTOR signaling pathways and reduced expression of granzyme B and IFN-γ. Finally, we observed that Stat5a mutant mice revealed more tumor growth upon injection of RMA-S tumor cell line. Overall, our results demonstrate that the W484G mutation in the linker domain of STAT5A is sufficient to compromise STAT5A function in NK-cell homeostasis, responsiveness, and tumoricidal function.

中文翻译：

小鼠STAT5A接头域中的点突变与NK细胞调节受损有关。

转录因子STAT5对外周NK细胞的存活，增殖和细胞毒性功能至关重要。STAT5是指两种高度相关的蛋白质，STAT5A和STAT5B。在这项研究中，我们证实了STAT5A亚型对于NK细胞的重要性。我们对Stat5a基因中偶然发生的化学诱导的W484G突变进行了表征，发现该突变与STAT5A蛋白表达的降低有关。仔细检查Stat5a突变小鼠的NK细胞亚群显示，NK细胞数量和成熟度显着降低。IL-15处理的Stat5a突变NK细胞显示出对STAT5和mTOR信号通路的诱导缺陷，并且颗粒酶B和IFN-γ的表达降低。最后，我们观察到Stat5a突变小鼠在注射RMA-S肿瘤细胞系后显示出更多的肿瘤生长。全面的，

更新日期：2019-10-08

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