Recent work has highlighted the importance of the immune system in regulating tissue physiology beyond host defense. Amongst their various functions, immunocytes are important regulators of tissue regeneration and homeostasis. In muscle, a tightly coordinated network of immunocytes and mesenchymal stromal cells (MSCs) is required for adequate skeletal muscle repair after acute injury or disease. Recent studies identified regulatory T cells (Tregs) as important players in regulating excessive inflammation and potentiating regeneration, but the extent of intercellular communications underlying their functions remains poorly understood. We used a combination of single-cell, computational, and experimental approaches to dissect the dynamic communication networks between muscle Tregs and MSCs in a time-resolved dataset of skeletal muscle injury. We found distinct ligand-receptor interaction pathways enriched in the different phases of repair. Using a combination of CRISPR-knockdown systems and genetic mouse models, we validated the requirement of different chemokine signaling pathways in the early recruitment of Tregs to injured muscle, and identified a novel role for IL-18 in inducing a regenerative Treg population and potentiating muscle repair. This work identifies novel regulatory pathways and can inform therapeutic approaches to treat muscle-related pathologies.
Dr. Muñoz-Rojas was born and raised in Mexico City. He studied Bioengineering at the University of Pennsylvania and completed his Ph.D. in Biomedical Engineering at Yale University with Dr. Kathryn Miller-Jensen, where he developed systems immunology tools to study macrophage polarization. He is currently a Postdoctoral Research Fellow at Harvard Medical School in the Department of Immunology in Dr. Diane Mathis and Christophe Benoist’s laboratory, where he studies the role of regulatory T cells in regulating tissue homeostasis and repair.