TNF-alpha Induces Macroautophagy and Regulates MHC Class II Expression in Human Skeletal Muscle Cells
2011 | journal article. A publication with affiliation to the University of Göttingen.
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TNF-alpha Induces Macroautophagy and Regulates MHC Class II Expression in Human Skeletal Muscle Cells
Keller, C. W. ; Fokken, C.; Turville, S. G.; Luenemann, A.; Schmidt, J. ; Münz, C. & Luenemann, J. D. (2011)
Journal of Biological Chemistry, 286(5) pp. 3970-3980. DOI: https://doi.org/10.1074/jbc.M110.159392
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- Authors
- Keller, Christian W. ; Fokken, Claudia; Turville, Stuart G.; Luenemann, Anna; Schmidt, Jens ; Münz, Christian; Luenemann, Jan D.
- Abstract
- Macroautophagy, a homeostatic process that shuttles cytoplasmic constituents into endosomal and lysosomal compartments, has recently been shown to deliver antigens for presentation on major histocompatibility complex (MHC) class II molecules. Skeletal muscle fibers show a high level of constitutive macroautophagy and express MHC class II molecules upon immune activation. We found that tumor necrosis factor-alpha (TNF-alpha), a monokine overexpressed in inflammatory myopathies, led to a marked up-regulation of macroautophagy in skeletal myocytes. Furthermore, TNF-alpha augmented surface expression of MHC class II molecules in interferon-gamma (IFN-gamma)-treated myoblasts. The synergistic effect of TNF-alpha and IFN-gamma on the induction of MHC class II surface expression was not reflected by higher intracellular human leukocyte antigen (HLA)-DR levels and was reversed by macroautophagy inhibition, suggesting that TNF-alpha facilitates antigen processing via macroautophagy for more efficient MHC class II loading. Muscle biopsies from patients with sporadic inclusion body myositis, a well defined myopathy with chronic inflammation, showed that over 20% of fibers that contained autophagosomes costained for MHC class II molecules and that more than 40% of double-positive muscle fibers had contact with CD4(+) and CD8(+) immune cells. These findings establish a mechanism through which TNF-alpha regulates both macroautophagy and MHC class II expression and suggest that macroautophagy-mediated antigen presentation contributes to the immunological environment of the inflamed human skeletal muscle.
- Issue Date
- 2011
- Journal
- Journal of Biological Chemistry
- ISSN
- 0021-9258