Formin-like 1 mediates effector T cell trafficking to inflammatory sites to enable T cell-mediated autoimmunity
- University of Colorado School of Medicine, United States
- National Jewish Health, United States
Abstract
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.
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The data generated and analysed in this study are included in the manuscript and/or supporting files.
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Funding
National Institute of Allergy and Infectious Diseases (R56AI105111)
- Jordan Jacobelli
National Institute of Allergy and Infectious Diseases (R01AI125553)
- Jordan Jacobelli
National Institute of Allergy and Infectious Diseases (R21AI119932)
- Rachel S Friedman
JDRF (5-2013-200)
- Rachel S Friedman
- Jordan Jacobelli
National Institute of Allergy and Infectious Diseases (T32AI007405)
- Scott B Thompson
- Monique M Waldman
- Miriam L Estin
National Multiple Sclerosis Society (PP1775)
- Jordan Jacobelli
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication. The content of this work is solely the responsibility of the authors and does not necessarily represent the official views of the NIH or other funding agencies.
Ethics
Animal experimentation: All experiments involving mice were approved by the Institutional Animal Care and Use Committees of National Jewish Health (Protocol #AS2811-01-23) and the University of Colorado School of Medicine (Protocol #000937). All efforts were made to minimize mouse suffering.
Copyright
© 2020, Thompson et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Formin-like 1 mediates effector T cell trafficking to inflammatory sites to enable T cell-mediated autoimmunity
eLife 9:e58046.
https://doi.org/10.7554/eLife.58046
