The actin remodeling protein cofilin is crucial for thymic αβ but not γ[delta] T-cell development

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 o...

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Hauptverfasser: Seeland, Isabel (VerfasserIn) , Xiong, Ying (VerfasserIn) , Orlik, Christian (VerfasserIn) , Arnold, Bernd (VerfasserIn) , Samstag, Yvonne (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: July 9, 2018
In: PLoS biology
Year: 2018, Jahrgang: 16, Heft: 7
ISSN:1545-7885
DOI:10.1371/journal.pbio.2005380
Online-Zugang:Verlag, Volltext: https://doi.org/10.1371/journal.pbio.2005380
Verlag, Volltext: https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.2005380
Volltext
Verfasserangaben:Isabel Seeland, Ying Xiong, Christian Orlik, Daniel Deibel, Sandra Prokosch, Günter Küblbeck, Beate Jahraus, Daniela De Stefano, Sonja Moos, Florian C. Kurschus, Bernd Arnold, Yvonne Samstag

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520 |a 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. 
650 4 |a Actins 
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650 4 |a Phosphorylation 
650 4 |a Small interfering RNAs 
650 4 |a T cells 
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