The overall goal of the research in the Villalta laboratory is directed towards understanding how immune cells contribute to tissue injury and repair in degenerative and autoimmune diseases. During these pathological conditions immune cells contribute to disease pathogenesis by promoting altered cellular states of chronic stress and inflicting injury on the target tissue through cytolytic mechanisms. Specialized subsets of immune regulatory cells also exist that are critical in orchestrating the resolution of inflammation and tissue repair through the suppression of effector immune cells and direct interactions with the tissue that promote regeneration. Although several studies have characterized immune cell subpopulations in muscle that possess either pro-injury or pro-reparative functions, little is known about the signals regulating these distinct functional programs. To address this lack in understanding our laboratory uses the mdx mouse model of Duchenne muscular dystrophy, which has provided the field an excellent system to investigate the role of immunity in muscular dystrophy and how immune cells contribute to muscle injury and repair.
Two broad aims of the research in the Villalta laboratory are i) to define and characterize the immune cell populations that contribute to muscle regeneration during chronic muscle injury (e.g. regulatory T cells, M2 macrophages and type 2 innate lymphoid cells), and ii) to determine the cellular and molecular basis of immune-mediated regulation of muscle regeneration following acute injury and during muscular dystrophy. Using methods from both the immunology and muscle physiology fields, our research contributes to our understanding of the cellular and molecular basis of immune-mediated muscle damage and repair. Our findings position the field with new information for the development of novel therapies to treat and cure human disease, and have translational implication in a number of clinical settings including immunological tolerance during gene therapy and regenerative medicine. We reported on the role of T regs in 2014: Villalta SA, Bluestone JA et al. Regulatory T cells suppress muscle inflammation and injury in muscular dystrophy. Sci Transl Med. 2014, 15:258.
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