Ena/VASP proteins regulate activated T-cell trafficking by promoting diapedesis during transendothelial migration
| Autor: | Rachel S. Friedman, Miriam L Estin, Marlie H. Fisher, Scott B Thompson, Jordan Jacobelli, Brianna Traxinger |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
CD4-Positive T-Lymphocytes Cell type T cell Integrin alpha4 T-Lymphocytes Motility macromolecular substances Biology CD49d Cell morphology Lymphocyte Activation 03 medical and health sciences 0302 clinical medicine medicine Cell Adhesion Animals Cell adhesion Cytoskeleton Inflammation Mice Knockout Multidisciplinary Chemotaxis Experimental autoimmune encephalomyelitis Microfilament Proteins Transendothelial and Transepithelial Migration medicine.disease Phosphoproteins Actins Cell biology Mice Inbred C57BL 030104 developmental biology medicine.anatomical_structure PNAS Plus Cell Adhesion Molecules 030215 immunology |
| Zdroj: | Proceedings of the National Academy of Sciences of the United States of America. 114(14) |
| ISSN: | 1091-6490 |
| Popis: | Vasodilator-stimulated phosphoprotein (VASP) and Ena-VASP-like (EVL) are cytoskeletal effector proteins implicated in regulating cell morphology, adhesion, and migration in various cell types. However, the role of these proteins in T-cell motility, adhesion, and in vivo trafficking remains poorly understood. This study identifies a specific role for EVL and VASP in T-cell diapedesis and trafficking. We demonstrate that EVL and VASP are selectively required for activated T-cell trafficking but are not required for normal T-cell development or for naive T-cell trafficking to lymph nodes and spleen. Using a model of multiple sclerosis, we show an impairment in trafficking of EVL/VASP-deficient activated T cells to the inflamed central nervous system of mice with experimental autoimmune encephalomyelitis. Additionally, we found a defect in trafficking of EVL/VASP double-knockout (dKO) T cells to the inflamed skin and secondary lymphoid organs. Deletion of EVL and VASP resulted in the impairment in α4 integrin (CD49d) expression and function. Unexpectedly, EVL/VASP dKO T cells did not exhibit alterations in shear-resistant adhesion to, or in crawling on, primary endothelial cells under physiologic shear forces. Instead, deletion of EVL and VASP impaired T-cell diapedesis. Furthermore, T-cell diapedesis became equivalent between control and EVL/VASP dKO T cells upon α4 integrin blockade. Overall, EVL and VASP selectively mediate activated T-cell trafficking by promoting the diapedesis step of transendothelial migration in a α4 integrin-dependent manner. |
| Databáze: | OpenAIRE |
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