The actin remodeling protein cofilin is crucial for thymic ?? but not ?? T-cell development.

ABSTRACT: 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 ?? 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 TCR? chain intracellularly, they completely lacked TCR? surface expression. In contrast, nf cofilin mice possessed normal numbers of ?? T cells. Their functionality was confirmed in the ?? T-cell-driven, imiquimod (IMQ)-induced, psoriasis-like murine model. Overall, this study not only highlights the importance of cofilin for early ?? T-cell development but also shows for the first time that an actin-binding protein is differentially involved in ?? versus ?? T-cell development.

SUBMITTER: Seeland I 

PROVIDER: S-EPMC6053251 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature