小柯机器人

美国加州大学洛杉矶分校Maureen A. Su和Timothy E. O’Sullivan小组发现，x连锁表观遗传调节因子UTX控制不同性别之间自然杀伤(NK)细胞的固有差异。这一研究成果于2023年3月16日发表在国际学术期刊《自然—免疫学》上。

研究人员发现虽然雄性小鼠的NK细胞数量增加，但与雌性小鼠和人类的NK细胞相比，它们的效应功能降低。这些差异不仅仅取决于性腺激素，因为它们在性腺切除的小鼠中持续存在。Kdm6a（编码蛋白UTX）是一种避免X失活的表观遗传调节因子，在雄性NK细胞中表达较低，并且雌性小鼠NK细胞内在UTX的缺失会增加了NK细胞数量并降低了其效应反应。

此外，具有NK细胞内在UTX缺陷的小鼠对小鼠巨细胞病毒的致死性增加。综合多组学分析揭示了UTX在调节染色质可及性和基因表达方面的关键作用，这对NK细胞稳态和效应功能至关重要。总的来说，这些数据表明UTX是调控NK细胞性别差异的关键分子决定因素。

据悉，病毒感染存在性别差异，男性通常比女性更容易感染。矛盾的是，男性抗病毒NK细胞的数量增加。

附：英文原文

Title: The X-linked epigenetic regulator UTX controls NK cell-intrinsic sex differences

Author: Cheng, Mandy I., Li, Joey H., Riggan, Luke, Chen, Bryan, Tafti, Rana Yakhshi, Chin, Scott, Ma, Feiyang, Pellegrini, Matteo, Hrncir, Haley, Arnold, Arthur P., OSullivan, Timothy E., Su, Maureen A.

Issue&Volume: 2023-03-16

Abstract: Viral infection outcomes are sex biased, with males generally more susceptible than females. Paradoxically, the numbers of antiviral natural killer (NK) cells are increased in males. We demonstrate that while numbers of NK cells are increased in male mice, they display decreased effector function compared to females in mice and humans. These differences were not solely dependent on gonadal hormones, because they persisted in gonadectomized mice. Kdm6a (which encodes the protein UTX), an epigenetic regulator that escapes X inactivation, was lower in male NK cells, while NK cell-intrinsic UTX deficiency in female mice increased NK cell numbers and reduced effector responses. Furthermore, mice with NK cell-intrinsic UTX deficiency showed increased lethality to mouse cytomegalovirus. Integrative multi-omics analysis revealed a critical role for UTX in regulating chromatin accessibility and gene expression critical for NK cell homeostasis and effector function. Collectively, these data implicate UTX as a critical molecular determinant of sex differences in NK cells.

DOI: 10.1038/s41590-023-01463-8

Source: https://www.nature.com/articles/s41590-023-01463-8

Nature Immunology：《自然—免疫学》，创刊于2000年。隶属于施普林格·自然出版集团，最新IF：31.25
官方网址：https://www.nature.com/ni/
投稿链接：https://mts-ni.nature.com/cgi-bin/main.plex