title: An Slfn2 mutation causes lymphoid and myeloid immunodeficiency due to loss of immune cell quiescence.
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.
authors.affiliation: Department of Genetics, The Scripps Research Institute, La Jolla, California, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Berger
authors.forename: Philippe
authors.initials: P
authors.lastname: Krebs
authors.forename: Karine
authors.initials: K
authors.lastname: Crozat
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Li
authors.forename: Ben A
authors.initials: BA
authors.lastname: Croker
authors.forename: Owen M
authors.initials: OM
authors.lastname: Siggs
authors.forename: Daniel
authors.initials: D
authors.lastname: Popkin
authors.forename: Xin
authors.initials: X
authors.lastname: Du
authors.forename: Brian R
authors.initials: BR
authors.lastname: Lawson
authors.forename: Argyrios N
authors.initials: AN
authors.lastname: Theofilopoulos
authors.forename: Yu
authors.initials: Y
authors.lastname: Xia
authors.forename: Kevin
authors.initials: K
authors.lastname: Khovananth
authors.forename: Eva Marie
authors.initials: EM
authors.lastname: Moresco
authors.forename: Takashi
authors.initials: T
authors.lastname: Satoh
authors.forename: Osamu
authors.initials: O
authors.lastname: Takeuchi
authors.forename: Shizuo
authors.initials: S
authors.lastname: Akira
authors.forename: Bruce
authors.initials: B
authors.lastname: Beutler
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000276:immunology; D001483:Base Sequence; D018797:Cell Cycle Proteins / Q000235:genetics* / Q000276:immunology*; D002469:Cell Separation; D005434:Flow Cytometry; D007153:Immunologic Deficiency Syndromes / Q000235:genetics* / Q000276:immunology*; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation; D010641:Phenotype; D015398:Signal Transduction / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D018797:Cell Cycle Proteins; C521352:schlafen-2 protein, mouse