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International Immunology Advance Access originally published online on September 6, 2004
International Immunology 2004 16(10):1535-1548; doi:10.1093/intimm/dxh155
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© 2004 The Japanese Society for Immunology

Modulation of T cell development and activation by novel members of the Schlafen (slfn) gene family harbouring an RNA helicase-like motif

Peter Geserick, Frank Kaiser, Uwe Klemm, Stefan H. E. Kaufmann and Jens Zerrahn

Department of Immunology, Max-Planck Institute for Infection Biology, Schumannstr. 21–22, 10117 Berlin, Germany

Correspondence to: J. Zerrahn; E-mail: zerrahn{at}mpiib-berlin.mpg.de

The regulatory networks governing development and differentiation of hematopoietic cells are incompletely understood. Members of the Schlafen (Slfn) protein family have been implicated in the regulation of cell growth and T cell development. We have identified and chromosomally mapped four new members, slfn5, slfn8, slfn9 and slfn10, which belong to a distinct subgroup within this gene family. The characteristic feature of these proteins is the presence of sequence motifs identifying them as distinct members of the superfamily I of DNA/RNA helicases. A significant role of these newly identified members in hematopoietic cell differentiation is suggested based on their differential regulation (i) in developing and activated T cells, (ii) in LPS or IFN{gamma} activated macrophages, (iii) upon IL6 or LIF driven terminal differentiation of myeloblastic M1 cells into macrophage-like cells, and (iv) in splenocytes of mice infected with Listeria monocytogenes. In contrast to wild-type cells, IRF-1 and IFN{alpha}/ßR deficient macrophages, although undergoing growth arrest, fail to upregulate slfn gene expression upon IFN{gamma} or LPS stimulation, respectively. Therefore, an essential participation in IFN{gamma} or LPS induced growth arrest appears unlikely. Likewise, ectopic expression of the newly identified slfn family members in fibroblasts did not reveal a general impact on growth control. In contrast, transgenic T-cell specific expression of a representative member of this new subfamily, slfn8, resulted in profoundly impaired T cell development and peripheral T cells showed a reduced proliferative potential. Thus, functional participation of slfn8 in the regulatory networks governing T cell development and growth appears to be cell type specific.

Keywords: cellular differentiation, gene regulation, macrophages, thymus, T lymphocytes

Transmitting editor: T. Hünig


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