Formin-like 1 mediates effector T cell trafficking to inflammatory sites to enable T cell-mediated autoimmunity
Scott B Thompson,
Adam M Sandor,
Victor Lui,
Jeffrey W Chung,
Monique M Waldman,
Robert A Long,
Miriam L Estin,
Jennifer L Matsuda,
Rachel S Friedman,
Jordan Jacobelli
Affiliations
Scott B Thompson
Department of Biomedical Research, National Jewish Health, Denver, United States; Department of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, United States
Adam M Sandor
Department of Biomedical Research, National Jewish Health, Denver, United States; Department of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, United States
Victor Lui
Department of Biomedical Research, National Jewish Health, Denver, United States; Department of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, United States
Jeffrey W Chung
Department of Biomedical Research, National Jewish Health, Denver, United States; Department of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, United States; Barbara Davis Center, University of Colorado School of Medicine, Aurora, United States
Monique M Waldman
Department of Biomedical Research, National Jewish Health, Denver, United States; Department of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, United States; Barbara Davis Center, University of Colorado School of Medicine, Aurora, United States
Robert A Long
Department of Biomedical Research, National Jewish Health, Denver, United States; Department of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, United States
Miriam L Estin
Department of Biomedical Research, National Jewish Health, Denver, United States; Department of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, United States
Jennifer L Matsuda
Department of Biomedical Research, National Jewish Health, Denver, United States; Department of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, United States
Rachel S Friedman
Department of Biomedical Research, National Jewish Health, Denver, United States; Department of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, United States; Barbara Davis Center, University of Colorado School of Medicine, Aurora, United States
Department of Biomedical Research, National Jewish Health, Denver, United States; Department of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, United States; Barbara Davis Center, University of Colorado School of Medicine, Aurora, United States
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.
