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

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

Research output: Contribution to journalArticlepeer-review

55 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)335-343
Number of pages9
JournalNature immunology
Volume11
Issue number4
DOIs
StatePublished - 2010

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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