title: SLy1 regulates T-cell proliferation during Listeria monocytogenes infection in a Foxo1-dependent manner.
abstract: Infection of mice with Listeria monocytogenes results in a strong T-cell response that is critical for an efficient defense. Here, we demonstrate that the adapter protein SLy1 (SH3-domain protein expressed in Lymphocytes 1) is essential for the generation of a fully functional T-cell response. The lack of SLy1 leads to reduced survival rates of infected mice. The increased susceptibility of SLy1 knock-out (KO) mice was caused by reduced proliferation of differentiated T cells. Ex vivo analyses of isolated SLy1 KO T cells displayed a dysregulation of Forkhead box protein O1 shuttling after TCR signaling, which resulted in an increased expression of cell cycle inhibiting genes, and therefore, reduced expansion of the T-cell population. Forkhead box protein O1 shuttles to the cytoplasm after phosphorylation in a protein complex including 14-3-3 proteins. Interestingly, we observed a similar regulation for the adapter protein SLy1, where TCR stimulation results in SLy1 phosphorylation and SLy1 export to the cytoplasm. Moreover, immunoprecipitation analyses revealed a binding of SLy1 to 14-3-3 proteins. Altogether, this study describes SLy1 as an immunoregulatory protein, which is involved in the generation of adaptive immune responses during L. monocytogenes infection, and provides a model of how SLy1 regulates T-cell proliferation.
authors: Department of Pharmacology and Experimental Therapy, Institute of Experimental and Clinical Pharmacology and Toxicology, Eberhard Karls University Hospitals and Clinics, Interfaculty Center of Pharmacogenomics and Drug Research, University of Tübingen, Tübingen, Germany.
authors: Daniel
authors: D
authors: Schäll
authors: Department of Pharmacology and Experimental Therapy, Institute of Experimental and Clinical Pharmacology and Toxicology, Eberhard Karls University Hospitals and Clinics, Interfaculty Center of Pharmacogenomics and Drug Research, University of Tübingen, Tübingen, Germany.
authors: Fee
authors: F
authors: Schmitt
authors: Institute of Medical Microbiology and Hospital Hygiene, Heinrich Heine University, Düsseldorf, Germany.
authors: Bernhard
authors: B
authors: Reis
authors: Institute of Medical Microbiology and Hospital Hygiene, Heinrich Heine University, Düsseldorf, Germany.
authors: Simone
authors: S
authors: Brandt
authors: Department of Pharmacology and Experimental Therapy, Institute of Experimental and Clinical Pharmacology and Toxicology, Eberhard Karls University Hospitals and Clinics, Interfaculty Center of Pharmacogenomics and Drug Research, University of Tübingen, Tübingen, Germany.|Institute of Medical Microbiology and Hospital Hygiene, Heinrich Heine University, Düsseldorf, Germany.
authors: Sandra
authors: S
authors: Beer-Hammer
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000276:immunology* / Q000378:metabolism; D033942:Adaptor Proteins, Vesicular Transport; D000818:Animals; D015153:Blotting, Western; D002454:Cell Differentiation / Q000276:immunology; D049109:Cell Proliferation; D004195:Disease Models, Animal; D005260:Female; D005434:Flow Cytometry; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors / Q000276:immunology* / Q000378:metabolism; D007113:Immunity, Innate / Q000276:immunology; D047468:Immunoprecipitation; D008089:Listeria monocytogenes; D008088:Listeriosis / Q000276:immunology* / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D014162:Transfection
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors; C467200:Foxo1 protein, mouse; C506091:SLY1 protein, mouse
keywords: Foxo1; Infection; Proliferation; SLy1; T cells