Department of Genetics, The Scripps Research Institute, La Jolla, California, USA.
Nat Immunol. 2010 Apr;11(4):335-43. doi: 10.1038/ni.1847. Epub 2010 Feb 28.
Here we describe a previously unknown form of inherited immunodeficiency revealed by an N-ethyl-N-nitrosourea-induced mutation called elektra. Mice homozygous for this mutation showed enhanced susceptibility to bacterial and viral infection and diminished numbers of T cells and inflammatory monocytes that failed to proliferate after infection and died via the intrinsic apoptotic pathway in response to diverse proliferative stimuli. They also had a greater proportion of T cells poised to replicate DNA, and their T cells expressed a subset of activation markers, suggestive of a semi-activated state. We positionally ascribe the elektra phenotype to a mutation in the gene encoding Schlafen-2 (Slfn2). Our findings identify a physiological role for Slfn2 in the defense against pathogens through the regulation of quiescence in T cells and monocytes.
在这里，我们描述了一种以前未知的遗传性免疫缺陷形式，这种形式是由 N-乙基-N-亚硝脲诱导的突变引起的，称为 elektra。这种突变的纯合子小鼠对细菌和病毒感染的敏感性增强，感染后 T 细胞和炎性单核细胞的数量减少，这些细胞无法增殖，并通过内在凋亡途径对多种增殖刺激物作出反应而死亡。它们还具有更大比例的准备复制 DNA 的 T 细胞，并且它们的 T 细胞表达了一组激活标记物，提示处于半激活状态。我们将 elektra 表型定位到编码 Schlafen-2（Slfn2）的基因突变上。我们的研究结果表明，Slfn2 通过调节 T 细胞和单核细胞的静止状态，在抵御病原体方面发挥了生理作用。
