FMNL1 promotes T cell extravasation and trafficking to sites of inflammation
| Autor: | Scott Beckett Thompson, Robert A. Long, Jeffrey W. Chung, Miriam L. Estin, Jordan Jacobelli |
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| Rok vydání: | 2018 |
| Předmět: | |
| Zdroj: | The Journal of Immunology. 200:102.19-102.19 |
| ISSN: | 1550-6606 0022-1767 |
| Popis: | To execute their effector function, activated T cells traffic through the blood stream to sites of inflammation. To enter tissues, T cells extravasate through the vascular endothelial cell wall by a process known as transendothelial migration (TEM). While many of the adhesion molecules and chemokine signaling pathways required for TEM have been previously characterized, little is known about how downstream cytoskeletal effectors mediate the mechanical forces and shape changes needed for T cell TEM. Formin-like 1 (FMNL1) is a terminal cytoskeletal effector directly involved in actin network remodeling. It has been associated with the formation of membrane protrusions that likely function in migration and cell-cell interactions, and is highly expressed by activated T cells. The goal of our study was to examine the role of FMNL1 in activated T cell extravasation and trafficking to sites of inflammation. While activated FMNL1 deficient T cells had normal migration in response to chemokine across 5μm pore transwell membranes, they displayed an impaired ability to migrate through more restrictive 3μm pores. In vitro time-lapse microscopy data suggest that FMNL1 deficient T cells have a reduced ability to complete TEM across brain endothelium. FMNL1 deficient T cells were also impaired in their ability to traffic to the inflamed central nervous system in vivo. Finally, adoptively transferred autoreactive FMNL1 deficient T cells were impaired in their ability to induce Experimental Autoimmune Encephalitis. Together these data suggest that FMNL1 is required for the efficient migration of activated T cells though restrictive endothelial barriers and may be a promising therapeutic target for regulating T cell trafficking in autoimmunity. |
| Databáze: | OpenAIRE |
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