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

doi:10.1038/ni.1847

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^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

70 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 language	English
Pages (from-to)	335-343
Number of pages	9
Journal	Nature Immunology
Volume	11
Issue number	4
DOIs	https://doi.org/10.1038/ni.1847
State	Published - 2010
Externally published	Yes

Bibliographical note

Funding Information:
We thank O. Milstein, J.F. Purton and K. Brandl for discussions; M.B.A. Oldstone (The Scripps Research Institute) for the Armstrong strain of LCMV; and C.D. Surh (The Scripps Research Institute) for monoclonal anti-IL-7 (M25). Supported by the European Molecular Biology Organization (M.B. and P.K.), the Swiss National Science Foundation (P.K.) and the US National Institutes of Health (PO1 AI070167-01).

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Berger, M., Krebs, P., Crozat, K., Li, X., Croker, B. A., Siggs, O. M., Popkin, D., Du, X., Lawson, B. R., Theofilopoulos, A. N., Xia, Y., Khovananth, K., Moresco, E. M. Y., Satoh, T., Takeuchi, O., Akira, S., & Beutler, B. (2010). An Slfn2 mutation causes lymphoid and myeloid immunodeficiency due to loss of immune cell quiescence. Nature Immunology, 11(4), 335-343. https://doi.org/10.1038/ni.1847

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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.",

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

note = "Funding Information: We thank O. Milstein, J.F. Purton and K. Brandl for discussions; M.B.A. Oldstone (The Scripps Research Institute) for the Armstrong strain of LCMV; and C.D. Surh (The Scripps Research Institute) for monoclonal anti-IL-7 (M25). Supported by the European Molecular Biology Organization (M.B. and P.K.), the Swiss National Science Foundation (P.K.) and the US National Institutes of Health (PO1 AI070167-01).",

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Berger, M, Krebs, P, Crozat, K, Li, X, Croker, BA, Siggs, OM, Popkin, D, Du, X, Lawson, BR, Theofilopoulos, AN, Xia, Y, Khovananth, K, Moresco, EMY, Satoh, T, Takeuchi, O, Akira, S & Beutler, B 2010, 'An Slfn2 mutation causes lymphoid and myeloid immunodeficiency due to loss of immune cell quiescence', Nature Immunology, vol. 11, no. 4, pp. 335-343. https://doi.org/10.1038/ni.1847

TY - JOUR

T1 - An Slfn2 mutation causes lymphoid and myeloid immunodeficiency due to loss of immune cell quiescence

AU - Berger, Michael

AU - Krebs, Philippe

AU - Crozat, Karine

AU - Li, Xiaohong

AU - Croker, Ben A.

AU - Siggs, Owen M.

AU - Popkin, Daniel

AU - Du, Xin

AU - Lawson, Brian R.

AU - Theofilopoulos, Argyrios N.

AU - Xia, Yu

AU - Khovananth, Kevin

AU - Moresco, Eva Marie Y.

AU - Satoh, Takashi

AU - Takeuchi, Osamu

AU - Akira, Shizuo

AU - Beutler, Bruce

N1 - Funding Information: We thank O. Milstein, J.F. Purton and K. Brandl for discussions; M.B.A. Oldstone (The Scripps Research Institute) for the Armstrong strain of LCMV; and C.D. Surh (The Scripps Research Institute) for monoclonal anti-IL-7 (M25). Supported by the European Molecular Biology Organization (M.B. and P.K.), the Swiss National Science Foundation (P.K.) and the US National Institutes of Health (PO1 AI070167-01).

PY - 2010

Y1 - 2010

N2 - 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.

AB - 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.

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

Abstract

Bibliographical note

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