title: Impaired immune responses and prolonged allograft survival in Sly1 mutant mice.
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 (SLY1(d)) protein is localized exclusively in the cytoplasm. B- and T-cell proliferation is attenuated and T-cell cytokine production is severely reduced. Sly1(d/d) mice exhibit reduced lymphoid 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 Sly1(d/d) mice. These results define SLY1 as an essential molecular component for the full activation of adaptive immunity.
authors.affiliation: Department of Surgery, Technische Universität München, Ismaninger Strasse 22, 81675 Munich, Germany.
authors.forename: Sandra
authors.initials: S
authors.lastname: Beer
authors.forename: Tanja
authors.initials: T
authors.lastname: Scheikl
authors.forename: Bernhard
authors.initials: B
authors.lastname: Reis
authors.forename: Norbert
authors.initials: N
authors.lastname: Hüser
authors.forename: Klaus
authors.initials: K
authors.lastname: Pfeffer
authors.forename: Bernhard
authors.initials: B
authors.lastname: Holzmann
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000276:immunology*; D033942:Adaptor Proteins, Vesicular Transport; D000595:Amino Acid Sequence; D000818:Animals; D000917:Antibody Formation / Q000235:genetics; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002467:Cell Nucleus / Q000378:metabolism; D049109:Cell Proliferation; D016207:Cytokines / Q000096:biosynthesis; D003593:Cytoplasm / Q000378:metabolism; D006085:Graft Survival / Q000235:genetics / Q000276:immunology*; D016027:Heart Transplantation / Q000276:immunology*; D008213:Lymphocyte Activation; D008221:Lymphoid Tissue / Q000254:growth & development; D051379:Mice; D008817:Mice, Mutant Strains; D008969:Molecular Sequence Data; D009154:Mutation; D019913:Nuclear Localization Signals / Q000235:genetics; D011948:Receptors, Antigen, T-Cell / Q000502:physiology; D012694:Serine / Q000235:genetics; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D014184:Transplantation, Homologous
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport; D016207:Cytokines; D019913:Nuclear Localization Signals; D011948:Receptors, Antigen, T-Cell; C506091:SLY1 protein, mouse; D012694:Serine