The actin remodeling protein cofilin is crucial for thymic αβ but not γδ T-cell development
| العنوان: | The actin remodeling protein cofilin is crucial for thymic αβ but not γδ T-cell development |
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| المؤلفون: | Beate Jahraus, Sonja Moos, Günter Küblbeck, Florian C. Kurschus, Sandra Prokosch, Daniel Deibel, Isabel Seeland, Daniela De Stefano, Ying Xiong, Bernd Arnold, Yvonne Samstag, Christian Orlik |
| المصدر: | PLoS Biology PLoS Biology, Vol 16, Iss 7, p e2005380 (2018) |
| بيانات النشر: | Public Library of Science, 2018. |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | 0301 basic medicine, Receptors, Antigen, T-Cell, alpha-beta, T-Lymphocytes, Jurkat cells, environment and public health, Immune Receptors, Biochemistry, White Blood Cells, Jurkat Cells, Mice, 0302 clinical medicine, Contractile Proteins, Spectrum Analysis Techniques, Short Reports, Animal Cells, Cell Movement, T-Lymphocyte Subsets, Medicine and Health Sciences, Gene Knock-In Techniques, Biology (General), Post-Translational Modification, Phosphorylation, Thymocytes, Immune System Proteins, T Cells, General Neuroscience, Stem Cells, Receptors, Antigen, T-Cell, gamma-delta, Transfection, Animal Models, Cofilin, Flow Cytometry, Cell biology, Thymus, medicine.anatomical_structure, Experimental Organism Systems, Actin Depolymerizing Factors, Spectrophotometry, 030220 oncology & carcinogenesis, Cytophotometry, Cellular Types, General Agricultural and Biological Sciences, Signal Transduction, Hematopoietic Progenitor Cells, Proline, QH301-705.5, T cell, Immune Cells, Immunology, Double negative, Mouse Models, macromolecular substances, Thymus Gland, Biology, Research and Analysis Methods, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, Model Organisms, medicine, Animals, Humans, Actin, Blood Cells, General Immunology and Microbiology, Actin remodeling, Biology and Life Sciences, Proteins, Cell Biology, Actins, T Cell Receptors, Cytoskeletal Proteins, 030104 developmental biology, Immune System, Mutation |
| الوصف: | 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. Author summary T cells are produced in the thymus and are critical to fighting infections and combating cancer. To move through the body and to fulfill their specific functions, T cells need to dynamically reshape their cell body. This requires remodeling the actin cytoskeleton using a plethora of actin-binding proteins, including cofilin. Whereas the majority of T cells use one type of cell membrane protein called αβ T cell receptor (TCR) to recognize their target, a minor population of T cells use a different type of receptors that are called γδTCR. The decision on whether thymocytes, the precursors of T cells, develop into αβTCR or γδTCR-bearing T cells takes place within the thymus. By replacing the cofilin gene with a nf copy, we identified an important role for cofilin in T-cell development. These mutant mice exhibited a severe thymus atrophy. Importantly, αβ T-cell development was severely affected, but the γδ T cells were unaffected in number and functional, as they were capable of responding to activation signal both in culture and inside the body. Overall, our study reveals the importance of cofilin in early αβ T-cell development and shows for the first time that an actin-binding protein is differentially involved in αβ versus γδ T-cell development. |
| اللغة: | English |
| تدمد: | 1545-7885 1544-9173 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::fea989faed7664bb705027289e17551e http://europepmc.org/articles/PMC6053251 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....fea989faed7664bb705027289e17551e |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15457885 15449173 |
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