TY - JOUR TI - Formin-like 1 mediates effector T cell trafficking to inflammatory sites to enable T cell-mediated autoimmunity AU - Thompson, Scott B AU - Sandor, Adam M AU - Lui, Victor AU - Chung, Jeffrey W AU - Waldman, Monique M AU - Long, Robert A AU - Estin, Miriam L AU - Matsuda, Jennifer L AU - Friedman, Rachel S AU - Jacobelli, Jordan A2 - Akhmanova, Anna A2 - Dustin, Michael L A2 - Morley, S Celeste VL - 9 PY - 2020 DA - 2020/06/08 SP - e58046 C1 - eLife 2020;9:e58046 DO - 10.7554/eLife.58046 UR - https://doi.org/10.7554/eLife.58046 AB - 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. KW - cell migration KW - cytoskeleton KW - T cell KW - autoimmunity KW - FMNL1 KW - actin JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -