Muscle-derived positive and negative regulators of the immune response.

Purpose Of Review: 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.

Recent Findings: 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.

Summary: 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.