Immunolocalization of FAS and FAS ligand in inflammatory myopathies

Apoptosis in idiopathic inflammatory myopathies with partial invasion; a role for CD8+ cytotoxic T cells?

“…The absence of FAS in fibres with apoptotic nuclei, which is in agreement with earlier studies [ 16 , 19 , 30 ], together with the presence of granzyme B + cells, strongly favours a cytotoxic mode of apoptosis induction rather than a FAS-mediated mechanism. Other proteins secreted by the CD8 + cytotoxic T cells, such as other granzymes [ 53 ] or other molecules [ 15 , 54 ] may be alternative, albeit less likely, candidates of inducing apoptosis.…”

“…The general effector mechanism mediated by cytotoxic CD8 + T-cells is to induce apoptosis, either by means of granzyme/perforin secretion or by binding of the FAS-ligand (FAS-L) to FAS receptors (hereafter called FAS) of target cells [ 10 – 13 ]. Expression of granzyme B and perforin in inflammatory cells [ 14 , 15 ], as well as the expression of FAS in muscle fibres [ 16 – 18 ], has been reported in inflammatory myopathies, but signs of apoptotic fibre nuclei have rarely been observed in fibres affected by partial invasion [ 19 , 20 ]. Overall, signs of apoptosis in IIM muscle fibres have, despite reports of its presence [ 20 , 21 ], been considered rare, and unlikely of importance for the pathogenesis [ 20 , 22 ].…”

“…Considering the main cytotoxic effector functions of the CD8 + T-cells, characteristically present in IBM and polymyositis, several studies have identified factors with potential to protect muscle from apoptosis [ 16 , 18 , 30 , 31 ]. The fact that muscle fibres do not normally express MHC I [ 32 ], but constitutionally HLA-G [ 33 ], and the rather uncommon occurrence of inflammatory muscle diseases, indicate a relative protected immunologic status of striated muscle.…”

The neurotrophin receptor p75NTR is induced on mature myofibres in inflammatory myopathies and promotes myotube survival to inflammatory stress

“…However, a recent study demonstrated that, although triggering Akt pathway and inhibiting atrogin-1, IGF-1 alone is not able to reverse muscle atrophy induced by inflammatory mediators [48]. Interestingly, while taking place in dystrophic muscle [49][50][51][52], myofibre apoptosis is not a major effector mechanism in inflammatory myopathies [53][54][55][56]. Overall, we identified a p75NTR-dependent survival pathway to inflammatory stress in differentiated muscle cells and speculate that the observed p75NTR upregulation on mature myofibres in inflamed muscle may deliver rescue signals from atrophy.…”

Cytokines and Chemokines as Regulators of Skeletal Muscle Inflammation: Presenting the Case of Duchenne Muscular Dystrophy

“…A small proportion of DMD muscle fibers express the corresponding receptor Fas [ 27 ]. Induction of both ligand and receptor could, unlike in idiopathic inflammatory myopathies [ 28 ], indicate an involvement of Fas/FasL—mediated apoptosis in DMD muscle atrophy and degeneration. TNF-like weak inducer of apoptosis (TWEAK; TNFSF12) is a major inducer of muscle wasting [ 29 ] and preventer of muscle regeneration [ 30 ].…”