The MRTFs are required for thymocyte trafficking and Treg-mediated immune tolerance
- 1The Francis Crick Institute
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 (MrtfabKOT animals). Positive selection, and development of MrtfabKOT regulatory (Treg), {gamma}{delta}, and NK T cells proceeded normally. Thymic egress was impaired, however, with mature T cells accumulating at the cortico-medullary junction, and in vitro MrtfabKOT thymocytes exhibited impaired cytoskeletal responses to S1P and migratory cytokines. MrtfabKOT mice were lymphopenic, with defective homeostatic proliferation and T cell homing to peripheral lymphoid organs. Although thymocyte negative selection was unaffected, MrtfabKOT animals develop autoimmune phenotypes in lacrimal gland and intestinal mucosa. Using the experimental colitis model, we show that these phenotypes reflect functional deficits in MrtfabKOT Treg 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 Treg function.
Related
- Do fungal pathogens exploit HLA-G-mediated immune tolerance?
- Rv2061c, a Putative F420-Dependent Oxidoreductase, is Required for Tolerance to Malachite Green and Other Antimicrobials and Oxidative Stress Protection in Mycobacterium tuberculosis
- Mechanistic Insights into MYO1C-Mediated Rhodopsin Trafficking and Rod Photoreceptor Homeostasis.
- ROP GTPases are required for YUC transcription and auxin-mediated root hair growth in Arabidopsis
- Gαq-mediated contact release is required for efficient mitochondrial quality control
BibTeX
@misc{costello2026mrtfs,
title = {{The MRTFs are required for thymocyte trafficking and Treg-mediated immune tolerance}},
author = {P. Costello and D. Maurice and M. Benito-Jardon and R. Treisman},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.02.756229},
url = {https://www.biorxiv.org/content/10.64898/2026.10.02.756229v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - The MRTFs are required for thymocyte trafficking and Treg-mediated immune tolerance
AU - P. Costello
AU - D. Maurice
AU - M. Benito-Jardon
AU - R. Treisman
PY - 2026
DA - 2026/10/02
PB - bioRxiv
DO - 10.64898/2026.10.02.756229
UR - https://www.biorxiv.org/content/10.64898/2026.10.02.756229v1
AB - 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 (MrtfabKOT animals). Positive selection, and development of MrtfabKOT regulatory (Treg), {gamma}{delta}, and NK T cells proceeded normally. Thymic egress was impaired, however, with mature T cells accumulating at the cortico-medullary junction, and in vitro MrtfabKOT thymocytes exhibited impaired cytoskeletal responses to S1P and migratory cytokines. MrtfabKOT mice were lymphopenic, with defective homeostatic proliferation and T cell homing to peripheral lymphoid organs. Although thymocyte negative selection was unaffected, MrtfabKOT animals develop autoimmune phenotypes in lacrimal gland and intestinal mucosa. Using the experimental colitis model, we show that these phenotypes reflect functional deficits in MrtfabKOT Treg 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 Treg function.
ER -