Impaired immune responses and prolonged allograft survival in Sly1 mutant mice

Sandra Beer, Tanja Scheikl, Bernhard Reis, Norbert Hüser, Klaus Pfeffer, Bernhard Holzmann

Research output: Contribution to journalArticlepeer-review

27 Scopus citations

Abstract

Adaptive immunity is crucial for protective host defense and the development of immunological disorders. SLY1 was recently identified as an X-chromosomal SH3 protein that is serine phosphorylated (Ser27) upon B- and T-cell receptor engagement. Here, we demonstrate that SLY1 is localized in the cytoplasm and the nucleus of immunocytes. We generated mice expressing a mutant version of SLY1 lacking Ser27 and a functional nuclear localization signal. The defective SLY1 (SLY1d) protein is localized exclusively in the cytoplasm. B- and T-cell proliferation is attenuated and T-cell cytokine production is severely reduced. Sly1d/d mice exhibit reduced lymplioid organ sizes, diminished marginal zone B-cell numbers, and severely impaired antibody responses against T-dependent and -independent antigens. Importantly, survival of semi-identical cardiac allografts was substantially prolonged in Sly1d/d mice. These results define SLY1 as an essential molecular component for the full activation of adaptive immunity.

Original languageEnglish
Pages (from-to)9646-9660
Number of pages15
JournalMolecular and Cellular Biology
Volume25
Issue number21
DOIs
StatePublished - Nov 2005

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