Formin-like 1 mediates effector T cell trafficking to inflammatory sites to enable T cell-mediated autoimmunity
| Autor: | Adam M. Sandor, Robert A Long, Jennifer L. Matsuda, Rachel S. Friedman, Monique M Waldman, Miriam L Estin, Scott B Thompson, Jeffrey W Chung, Victor Lui, Jordan Jacobelli |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Naive T cell cell migration Mouse QH301-705.5 Lymphocyte T cell Science T-Lymphocytes Cell Formins General Biochemistry Genetics and Molecular Biology Cell Line FMNL1 Lymphatic System 03 medical and health sciences Mice 0302 clinical medicine Immunology and Inflammation Cell Movement medicine Animals Biology (General) Inflammation Mice Knockout General Immunology and Microbiology biology Effector General Neuroscience autoimmunity Endothelial Cells Cell migration cytoskeleton General Medicine Cell Biology Acquired immune system Cell biology 030104 developmental biology medicine.anatomical_structure 030220 oncology & carcinogenesis biology.protein Medicine actin Research Article |
| Zdroj: | eLife eLife, Vol 9 (2020) |
| ISSN: | 2050-084X |
| Popis: | Lymphocyte migration is essential for the function of the adaptive immune system, and regulation of T cell entry into tissues is an effective therapy in autoimmune diseases. Little is known about the specific role of cytoskeletal effectors that mediate mechanical forces and morphological changes essential for migration in complex environments. We developed a new Formin-like-1 (FMNL1) knock-out mouse model and determined that the cytoskeletal effector FMNL1 is selectively required for effector T cell trafficking to inflamed tissues, without affecting naïve T cell entry into secondary lymphoid organs. Here, we identify a FMNL1-dependent mechanism of actin polymerization at the back of the cell that enables migration of the rigid lymphocyte nucleus through restrictive barriers. Furthermore, FMNL1-deficiency impairs the ability of self-reactive effector T cells to induce autoimmune disease. Overall, our data suggest that FMNL1 may be a potential therapeutic target to specifically modulate T cell trafficking to inflammatory sites. |
| Databáze: | OpenAIRE |
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