An Slfn2 mutation causes lymphoid and myeloid immunodeficiency due to loss of immune cell quiescence

作者：Berger Michael; Krebs Philippe; Crozat Karine; Li Xiaohong; Croker Ben A; Siggs Owen M; Popkin Daniel; Du Xin; Lawson Brian R; Theofilopoulos Argyrios N; Xia Yu; Khovananth Kevin; Moresco Eva Marie Y; Satoh Takashi; Takeuchi Osamu; Akira Shizuo; Beutler Bruce^*

来源：Nature Immunology, 2010, 11(4): 335-U55.

DOI：10.1038/ni.1847

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.

• 出版日期2010-4