Formin-like 1 mediates effector T cell trafficking to inflammatory sites to enable T cell-mediated autoimmunity.
Elife
; 92020 06 08.
Article
en En
| MEDLINE
| ID: mdl-32510333
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.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Linfocitos T
/
Autoinmunidad
/
Movimiento Celular
/
Forminas
/
Inflamación
Límite:
Animals
Idioma:
En
Revista:
Elife
Año:
2020
Tipo del documento:
Article
País de afiliación:
Estados Unidos