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CRISPRi查发现SON和MAP4K1是先天性淋巴细胞中III型细胞因子表达的调节者

Rachel A Brown^1,2, Andrew W Dangel¹, Ankita Saini^1,2

¹Department of Microbial Infection and Immunity, The Ohio State University, Columbus, OH, 43210, USA.

bioRxiv : the preprint server for biology

|August 20, 2025

概括

一个全基因组查发现了免疫细胞中互白素-22 (IL-22) 和IL-17的新调节剂. 了解这些因素,如SON和MAP4K1,为免疫媒介疾病提供了潜在的治疗点.

科学领域:

免疫学
分子生物学
遗传学

背景情况:

干白素 (IL-22) 和IL-17是粘膜免疫和宿主防御的关键细胞因子.
IL-22/IL-17的失调与自身免疫性疾病,慢性炎症和癌症有关.
识别IL-22/IL-17生产的调节剂是开发新疗法的关键.

研究的目的:

确定调节IL-22和IL-17表达的新型遗传因素.
研究已识别的因素在III型免疫反应中的作用.
探索免疫媒介疾病的潜在治疗点.

主要方法:

在小鼠III型先天性淋巴细胞 (ILC3) 模型 (MNK3) 中进行全基因组CRISPR抑制 (CRISPRi) 查.
用IL-23和IL-1b刺激MNK3细胞.
新型因子的验证,包括SON和MAP4K1 (HPK1).

主要成果:

查发现了已知和新的IL-22/IL-17表达调节剂.
在转录和RNA处理水平上发现SON会损害IL-12RB1的表达.
对于IL-22的表达,MAP4K1的耗尽是必要的,并导致IL-17和IFN-g的同时表达.

结论:

这项研究扩大了对控制III型免疫反应的因素的理解.
SON和MAP4K1被确定为IL-22/IL-17的新调节剂.
这些发现为免疫媒介疾病中的IL-22/IL-17调节提供了新的点.

关键词:

在CRISPRi中一个IL-22 其他国家其他类型 SON DNA 结合蛋白

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相关概念视频

CRISPR and crRNAs

CRISPR and crRNAs

Bacteria and archaea are susceptible to viral infections just like eukaryotes; therefore, they have developed a unique adaptive immune system to protect themselves. Clustered regularly interspaced short palindromic repeats and CRISPR-associated proteins (CRISPR-Cas) are present in more than 45% of known bacteria and 90% of known archaea.
The CRISPR-Cas system stores a copy of foreign DNA in the host genome and uses it to identify the foreign DNA upon reinfection. CRISPR-Cas has three different...