Regulation of class I MHC expression in skeletal muscle: deleterious effect of aberrant expression on myogenesis.

Aberrant expression of class I major histocompatibility complex (MHC) occurs on myofibers in inflammatory myopathies. The mechanisms responsible for such expression are unknown. Here we show that class I MHC expression is developmentally regulated during muscle regeneration with significant levels only in myoblasts. Injection of gamma-IFN plasmid leads to muscle inflammation, induction of class I MHC in regenerating, but not mature myofibers, and attenuation of regeneration. Gene transfer of class I MHC in vivo and in vitro also attenuates muscle differentiation. Thus, cytokines may contribute to the pathogenesis of inflammatory myopathies by upregulating class I MHC and leading to deleterious effects on muscle repair.