Article
Activated dendritic cells modulate proliferation and differentiation of human myoblasts
Registro en:
LADISLAU, Leandro; et al. Activated dendritic cells modulate proliferation and differentiation of human myoblasts. Cell Death and Disease, v.9:551, 14p, 2018.
2041-4889
10.1038/s41419-018-0426-z
Autor
Ladislau, Leandro
Portilho, Débora M.
Courau, Tristan
Solares-Pérez, Alhondra
Negroni, Elisa
Lainé, Jeanne
Klatzmann, David
Bonomo, Adriana
Allenbach, Yves
Benveniste, Olivier
Riederer, Ingo
Savino, Wilson
Mouly, Vincent
Butler-Browne, Gillian
Benjamim, Claudia F.
Resumen
Idiopathic Inflammatory Myopathies (IIMs) are a heterogeneous group of autoimmune diseases affecting skeletal muscle tissue homeostasis. They are characterized by muscle weakness and inflammatory infiltration with tissue damage. Amongst the cells in the muscle inflammatory infiltration, dendritic cells (DCs) are potent antigen-presenting and key components in autoimmunity exhibiting an increased activation in inflamed tissues. Since, the IIMs are characterized by the focal necrosis/regeneration and muscle atrophy, we hypothesized that DCs may play a role in these processes. Due to the absence of a reliable in vivo model for IIMs, we first performed co-culture experiments with immature DCs (iDC) or LPS-activated DCs (actDC) and proliferating myoblasts or differentiating myotubes. We demonstrated that both iDC or actDCs tightly interact with myoblasts and myotubes, increased myoblast proliferation and migration, but inhibited myotube differentiation. We also observed that actDCs increased HLA-ABC, HLA-DR, VLA-5, and VLA-6 expression and induced cytokine secretion on myoblasts. In an in vivo regeneration model, the co-injection of human myoblasts and DCs enhanced human myoblast migration, whereas the absolute number of human myofibres was unchanged. In conclusion, we suggest that in the early stages of myositis, DCs may play a crucial role in inducing muscle-damage through cell-cell contact and inflammatory cytokine secretion, leading to muscle regeneration impairment.