Muscle-derived positive and negative regulators of the immune response

Recent characterization of the expression and functioning of muscle-derived positive and negative regulators of the immune response will be highlighted in view of the concept that muscle cells can act as facultative antigen-presenting cells and should be considered as active participants rather than passive targets of immune reactions.

Although lacking detectable major histocompatibility complex expression under physiologic conditions, under pathologic conditions muscle cells can express a variety of immunologically important molecules. Advances were made in characterizing the expression and functioning of classical and nonclassical major histocompatibility complex, adhesion, and costimulatory molecules. Muscle-related expression of the B7-family member called the inducible costimulatory signal ligand was identified as an important costimulatory signal for muscle immune interactions. In contrast, inducible expression of B7-H1 (PD-L1) and the nonclassical major histocompatibility complex molecule human leukocyte antigen-G were identified as relevant immune-inhibitory pathways.

The recent identification of muscle-derived positive and negative signals has broad implications for understanding the active role of muscle in modulating muscle-immune interactions: these signals could modify the immune response against muscle fibers in cell-mediated injury in autoimmune muscle disorders or in various muscle infections. Furthermore, they could modulate the immune responses after protein-based or DNA-based vaccinations and influence muscle-directed antigen-specific and nonantigen-specific immune responses in either condition.