Interactions between skeletal muscle and the immune system. A major project in our lab concerns the pathophysiology of muscular dystrophy (dystrophinopathy). Our research has shown that the immune system plays an important role in influencing the severity of muscular dystrophy, and that immune-based interventions can significantly reduce dystrophic muscle pathology and promote muscle regeneration. Our continuing efforts are directed toward identifying the key effector cells and molecules involved in influencing the course of the disease, and examining the interplay between those effectors. Our technical approaches include the generation and analysis of transgenic, dystrophic mice so that the effects of increased or decreased expression of selected effector molecules can be assessed. We also examine the systemic effects of experimental depletions of selected immune cell populations and the efficacy of selected, pharmaceutical interventions on the progress of the disease. In other studies, we are studying the mechanisms through which the immune system influences the wasting of skeletal muscle that occurs during aging, a process called sarcopenia. We are particularly interested in identifying the mechanisms through which specific populations of myeloid cells affect muscle wasting and regeneration, and identifying strategies to slow the wasting process.
A selected list of publications:
Villalta, S.A., Deng, B., Rinaldi, C., Wehling-Henricks, M. and J. G. Tidball IFNγ promotes muscle damage in the mdx mouse model of Duchenne muscular dystrophy by suppressing M2 macrophage activation and inhibiting muscle cell proliferation, J. Immunol, 2011; 187: 5419-5428 .
Villalta, S.A., Rinaldi, C., Deng, B., Liu, G., Fedor, B. and J. G. Tidball Interleukin-10 reduces the pathology of mdx muscular dystrophy by deactivating M1 macrophages and modulating macrophage phenotype, Human Molecular Genetics , 2011; 20: 790-805.
Wehling-Henricks, M. and J.G. Tidball Neuronal nitric oxide synthase-rescue of dystrophin/utrophin double knockout mice does not require nNOS localization to the cell membrane, PLoS One , 2011; 6: e25071.
Sakellariou, G.K., Pye, D., Vasilaki, A., Zibrik, L., Palomero, J., Kabayo, T., McArdle, F., Van Remmen, H., Richardson, A., Tidball, J.G., McArdle, A. and M. J. Jackson Role of superoxide-nitric oxide interactions in the accelerated age-related loss of muscle mass in mice lacking Cu,Zn superoxide dismutase, Aging Cell , 2011; 10: 749-760.
Wehling-Henricks, M., M. C. Jordan, T. Gotoh, W. W. Grody, K. P. Roos and J. G. Tidball Arginine metabolism by macrophages promotes cardiac and muscle fibrosis in mdx muscular dystrophy, PLoS One, 2010; 5(5): e10763. doi:10.1371/journal.pone.0010763.
Tidball, J.G. and S.A. Villalta Interactions between muscle and the immune system regulate muscle growth and regeneration, Amer. J. Physiol, 2010; 298: R1173-1187.
Perez Antonio L, Bachrach Estanislao, Illigens Ben M W, Jun Susan J, Bagden Eric, Steffen Leta, Flint Alan, McGowan Francis X, Del Nido Pedro, Montecino-Rodriguez Enca, Tidball James G, Kunkel Louis M CXCR4 enhances engraftment of muscle progenitor cells
Muscle & nerve, 2009; 40(4): 562-72.
Tidball, J.G. and M. Wehling-Henricks Inflammatory mechanisms in genetic neuromuscular disorders, Inflammatory and autoimmune disorders of the nervous system in children, 2009; 455-479.
Wehling-Henricks, M., M. Oltmann, C. Rinaldi, K. H. Myung, and J. G. Tidball Loss of positive allosteric interactions between neuronal nitric oxide synthase and phosphofructokinase contributes to defects in glycolysis and increased fatigability in muscular dystrophy, Human Molecular Genetics, 2009; 18: 3439-3451.
Deng, B., D. Glanzman and J.G. Tidball Nitric oxide generated by muscle corrects defects in hippocampal neurogenesis and neural differentiation caused by muscular dystrophy, Journal of Physiology, 2009; 587: 1769-1778.
Tidball, J.G. and S.A. Villalta Nitric oxide may prompt calcium leakage in dystrophic muscle, Nature Medicine, 2009; 15: 243-244.
Villalta, S.A., H.X. Nguyen, B. Deng, T. Gotoh and J.G. Tidball Shifts in macrophage phenotypes and macrophage competition for arginine metabolism affect the severity of muscle pathology in muscular dystrophy, Human Molecular Genetics, 2009; 18: 482-496.
Tidball, J.G. Inflammation in skeletal muscle regeneration, Skeletal muscle repair and regeneration, 2008; 243-268.
Wehling-Henricks, M., Sokolow, S., Lee, J.J., Myung, K.H., Villalta, A., and J.G. Tidball Major basic protein-1 promotes fibrosis of dystrophic muscle and attenuates the cellular immune response in muscular dystrophy, Human Molecular Genetics, 2008; 17:2280-2292: .
Hao, M., K. Akrami, K. Wei, C. De Diego, N. Che, J.H. Ku, J.G. Tidball, M.C. Graves, P.B. Shieh and F. Chen Muscleblind-like 2 (Mbnl2) -deficient mice as a model for myotonic dystrophy, Developmental Dynamics, 2008; 237: 403-410.
Acharyya, S., S.A. Villalta, N. Bakkar, T. Bupha-Intr, P.M.L. Janssen, M. Carathers, M. Karin, Z. Li, A. Beg, S. Ghosh, Z. Sahenk, M. Weinstein, K.L. Gardner, J.A. Rafael-Fortney, J.G. Tidball, A.S. Baldwin and D.C. Guttridge IKK/NF-kB signaling interplay in macrophages and myofibers promotes muscle wasting in Duchenne muscular dystrophy, Journal of Clinical Investigation, 2007; 117: 889-901.
Acharyya Swarnali, Villalta S Armando, Bakkar Nadine, Bupha-Intr Tepmanas, Janssen Paul M L, Carathers Micheal, Li Zhi-Wei, Beg Amer A, Ghosh Sankar, Sahenk Zarife, Weinstein Michael, Gardner Katherine L, Rafael-Fortney Jill A, Karin Michael, Tidball James G, Baldwin Albert S, Guttridge Denis C Interplay of IKK/NF-kappaB signaling in macrophages and myofibers promotes muscle degeneration in Duchenne muscular dystrophy
The Journal of clinical investigation, 2007; 117(4): 889-901.
Tidball, J.G. and M. Wehling-Henricks Macrophages promote muscle membrane repair and muscle fiber growth and regeneration during modified muscle loading in mice in vivo, Journal of Physiology, 2007; 578.1: 327-336.
Pfister, K., J. Radons, J.G. Tidball, M. Pfeifer, L. Freitag, H-J. Feldmann, V. Milani, R. Issels and G. Multhoff Patient survival by Hsp70 membrane-phenotype: association with different routes of metastasis, Cancer, 2007; 110: 926-35.
Chang, W., S. Iannaccone, K. Lau, B. Masters, T. McCabe K. McMillan, R. Padre, M.J. Spencer, J.G. Tidball and J.T. Stull Neuronal nitric oxide synthase and dystrophin-deficient muscular dystrophy, Proc. Natl. Acad. Sci. USA, 1996; 93: 9142-47.