Year: 2026
Type: preprint
Abstract: ABSTRACT The MRTFs (myocardin-related transcription factors) are essential for effective cytoskeletal function during differentiation and development. To investigate the role played by the MRTFs in T cell development and function we inactivated Mrtfb in Mrtfa -null mice at the DN2 stage ( Mrtfab KO T animals). Positive selection, and development of Mrtfab KO T regulatory (T reg ), γδ, and NK T cells proceeded normally. Thymic egress was impaired, however, with mature T cells accumulating at the cortico-medullary junction, and in vitro Mrtfab KO T thymocytes exhibited impaired cytoskeletal responses to S1P and migratory cytokines. Mrtfab KO T mice were lymphopenic, with defective homeostatic proliferation and T cell homing to peripheral lymphoid organs. Although thymocyte negative selection was unaffected, Mrtfab KO T animals develop autoimmune phenotypes in lacrimal gland and intestinal mucosa. Using the experimental colitis model, we show that these phenotypes reflect functional deficits in Mrtfab KO T T reg cells. Our findings show that MRTF-SRF signalling plays an unanticipated role in thymocyte egress and immune tolerance, and reveal a role of the MRTFs in T reg function.
Institution: The Francis Crick Institute
Language: English
Topic: T-cell and B-cell Immunology
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: green
Awards: G1059022183, G1327616111, G2346338827
OpenAlex ID: W7221097932