Abstract
The neuregulins are a family of epidermal growth factors necessary for nervous system development. Neuregulins signal via the epidermal growth factor family of tyrosine kinase receptors (ErbB1, ErbB2, ErbB3, and ErbB4). ErbB3 and ErbB4 bind neuregulins with high affinity, although to transduce an effective signal ErbB3 and ErbB4 must heterodimerize with ErbB1 or ErbB2 after ligand binding. Both ErbB3 and ErbB4 heterodimerize primarily with ErbB2. Using the Theiler’s murine encephalomyelitis virus (TMEV) model of demyelinating disease, we infected FVB/nJ mice and we assessed the kinetics and expression of ErbB2 in the spinal cord of TMEV-infected mice early and late in the course of the development of demyelinating lesions. The data demonstrate that ErbB2, but not ErbB1, is upregulated in the spinal cord of TMEV-infected FVB/nJ mice in the early phase of demyelinating disease. Interestingly, cells of the immune system (T cells, B cells, and macrophages) express ErbB2, and immunoreactivity to ErbB2 increases upon stimulation of the cells with Concanavalin A. Together, these data suggest that neuregulins may interact with infiltrating immune cells, which are well-described participants in the pathology observed in TMEV-induced demyelination.