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RESEARCH PRODUCT
The actin remodeling protein cofilin is crucial for thymic αβ but not γδ T-cell development
Beate JahrausSonja MoosGünter KüblbeckFlorian C. KurschusSandra ProkoschDaniel DeibelIsabel SeelandDaniela De StefanoYing XiongBernd ArnoldYvonne SamstagChristian Orliksubject
0301 basic medicineReceptors Antigen T-Cell alpha-betaT-LymphocytesJurkat cellsenvironment and public healthImmune ReceptorsBiochemistryWhite Blood CellsJurkat CellsMice0302 clinical medicineContractile ProteinsSpectrum Analysis TechniquesShort ReportsAnimal CellsCell MovementT-Lymphocyte SubsetsMedicine and Health SciencesGene Knock-In TechniquesBiology (General)Post-Translational ModificationPhosphorylationThymocytesImmune System ProteinsT CellsGeneral NeuroscienceStem CellsReceptors Antigen T-Cell gamma-deltaTransfectionAnimal ModelsCofilinFlow CytometryCell biologyThymusmedicine.anatomical_structureExperimental Organism SystemsActin Depolymerizing FactorsSpectrophotometry030220 oncology & carcinogenesisPhosphorylationCytophotometryCellular TypesGeneral Agricultural and Biological SciencesSignal TransductionHematopoietic Progenitor CellsProlineQH301-705.5T cellImmune CellsImmunologyDouble negativeMouse Modelsmacromolecular substancesThymus GlandBiologyResearch and Analysis MethodsGeneral Biochemistry Genetics and Molecular Biology03 medical and health sciencesModel OrganismsmedicineAnimalsHumansActinBlood CellsGeneral Immunology and MicrobiologyActin remodelingBiology and Life SciencesProteinsCell BiologyActinsT Cell ReceptorsCytoskeletal Proteins030104 developmental biologyImmune SystemMutationdescription
Cofilin is an essential actin remodeling protein promoting depolymerization and severing of actin filaments. To address the relevance of cofilin for the development and function of T cells in vivo, we generated knock-in mice in which T-cell–specific nonfunctional (nf) cofilin was expressed instead of wild-type (WT) cofilin. Nf cofilin mice lacked peripheral αβ T cells and showed a severe thymus atrophy. This was caused by an early developmental arrest of thymocytes at the double negative (DN) stage. Importantly, even though DN thymocytes expressed the TCRβ chain intracellularly, they completely lacked TCRβ surface expression. In contrast, nf cofilin mice possessed normal numbers of γδ T cells. Their functionality was confirmed in the γδ T-cell–driven, imiquimod (IMQ)-induced, psoriasis-like murine model. Overall, this study not only highlights the importance of cofilin for early αβ T-cell development but also shows for the first time that an actin-binding protein is differentially involved in αβ versus γδ T-cell development.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2018-07-01 | PLoS Biology |