OBJECTIVE: Muscle regeneration is a hallmark of the @entity5442 ( @entity5442 ), a group of @entity792 that are characterized by leukocyte infiltration and dysfunction of the skeletal muscle. Despite detailed studies describing the clinical and histopathologic features of @entity5442 , the immunopathogenesis of these disorders remains undefined. The aim of this study was to investigate the immunopathologic processes of @entity792 in experimental @entity19 models. METHODS: Expression of the autoantigen @entity68587 ( @entity68587 ) was analyzed in @entity19 with acutely injured or dystrophic muscles, in inflammatory leukocytes, and in purified satellite cells. Anti- @entity68587 antibodies and @entity5442 induction were assessed in @entity19 after @entity121 and immunization with apoptotic satellite cells or C2C12 myoblasts, in the presence or absence of the @entity6439 ( @entity6439 ) agonist R848. RESULTS: @entity121 , leukocyte infiltration, and myofiber regeneration induced by toxic agents (cardiotoxin or @entity653 ) or promoted by genetic disruption of the a-sarcoglycan/dystrophin complex in @entity19 were uniformly associated with up-regulated expression of @entity68587 . Although regenerating myofibers and purified satellite cells are known to show increased expression of @entity68587 in these settings, anti- @entity68587 antibodies were not detectable. However, intramuscular immunization with ultraviolet B-irradiated, @entity68587 -expressing apoptotic myoblasts in the presence of R848 triggered the production of anti- @entity68587 IgG antibodies as well as persistent lymphocyte infiltration and prolonged/delayed muscle regeneration. Conversely, intramuscular administration of R848 alone or in combination with living or postapoptotic/ @entity39 myoblasts failed to generate this @entity5442 phenotype. CONCLUSION: In the presence of TLR/adjuvant signals and underlying @entity121 , apoptotic myogenic precursors expressing high levels of autoantigen can provoke autoantibody formation and lymphocytic infiltration of muscle tissue, effectively replicating the features of IIM.

Required role of apoptotic myogenic precursors and toll-like receptor stimulation for the establishment of @entity792 in experimental XXXX models.

@entity121 :: ('MESH:D009135', 'Disease') :: ['Muscle necrosis', 'muscle injury'] @entity5442 :: ('MESH:D009220', 'Disease') :: ['IIMs', 'myositis', 'idiopathic inflammatory myopathies'] @entity39 :: ('MESH:D009336', 'Disease') :: ['necrotic'] @entity19 :: ('10090', 'Species') :: ['mice', 'murine'] @entity653 :: ('MESH:D005990', 'Chemical') :: ['glycerol'] @entity68587 :: ('70791(Tax:10090)', 'Gene') :: ['histidyl-transfer RNA synthetase', 'HisRS'] @entity792 :: ('MESH:D001327', 'Disease') :: ['autoimmune disorders', 'autoimmune myositis'] @entity6439 :: ('170743(Tax:10090)', 'Gene') :: ['TLR-7', 'Toll-like receptor 7']
@entity19 :: (10090,Species) :: ['murine']
