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
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
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
/ßR deficient macrophages, although undergoing growth arrest, fail to upregulate slfn gene expression upon IFN or LPS stimulation, respectively. Therefore, an essential participation in IFN 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
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