Immunological Behavior Analysis of Muscle Cells under IFN‐γ Stimulation in Vitro and in Vivo

Abstract

Muscle cells could serve as antigen‐presenting cells, and participate in the activation of immune response. Immunological characteristics of muscle cells, and their capacities to equip themselves with immunorelevant molecules, remain to be elucidated. In this study, we investigated the immunological properties of myoblasts and differentiated myotubes in vitro and in vivo, under the IFN‐γ induced inflammatory condition. We found that the fused C₂C₁₂ myotubes are more sensitive to inflammatory stimulation, and significantly up‐regulated the expression levels of MHC‐I/II and TLR3/7 molecules, than that of proliferated myoblasts. As well, some co‐stimulatory/‐inhibitory molecules, including CD40, CD86, ICAM‐I, ICOS‐L and PD‐L1, were prominently up‐regulated in IFN‐γ induced myotubes. Notably, we detected the protein levels of ASC, NLRP3 and Caspase‐1 increased in stimulated myotubes, and IL‐1β in cell culture supernatant, implying the activation of NLRP3 inflammasomes in IFN‐γ treated myotubes. The pro‐inflammatory cytokines and chemokines mRNA levels in IFN‐γ induced C₂C₁₂ myotubes and myoblasts, involving IL‐1, IL‐6 and MCP‐1, increased markedly. T cell activation test further verified IFN‐γ induced C₂C₁₂ myotubes prompt to the proliferation of the splenic CD4⁺ and CD8⁺ T cells. In Cardiotoxin‐damaged tibialis anterior (TA) muscle, some regenerated myofibers expressed both MHC class I and class II molecules under IFN‐γ enhanced inflammatory condition. Thus, our work demonstrates that muscle cells are active participants of local immune reactions.