An Slfn2 mutation causes lymphoid and myeloid immunodeficiency due to loss of immune cell quiescence.
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.
Berger
Michael
M
Department of Genetics, The Scripps Research Institute, La Jolla, California, USA.
Krebs
Philippe
P
Crozat
Karine
K
Li
Xiaohong
X
Croker
Ben A
BA
Siggs
Owen M
OM
Popkin
Daniel
D
Du
Xin
X
Lawson
Brian R
BR
Theofilopoulos
Argyrios N
AN
Xia
Yu
Y
Khovananth
Kevin
K
Moresco
Eva Marie
EM
Satoh
Takashi
T
Takeuchi
Osamu
O
Akira
Shizuo
S
Beutler
Bruce
B
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*
D018797:Cell Cycle Proteins; C521352:schlafen-2 protein, mouse