About this Research Topic
The idiopathic inflammatory myopathies (IIM) represent a group of systemic autoimmune disorders in which muscle is inappropriately targeted for immune-mediated destruction. Extra-muscular complications may involve the skin, joints, vasculature, and lungs, with significant impact on morbidity and mortality. Current therapy is effective, but requires the use of potent immunosuppressive agents that are relatively non-specific and carry great risk of side effects such as infection. Based on these considerations and gaps in our understanding of disease pathogenesis, there is a clear need for expanded research and new disease models to facilitate development of more targeted therapy in this potentially devastating disease process.
Although IIM serves as a model of systemic autoimmunity, its relative rarity (estimated prevalence of 1 in 50,000) has complicated studies involving human cells/tissues. There is an extreme paucity of in vitro models capable of replicating many of the key cellular interactions that ultimately dictate immune infiltration of target tissues such as muscle and lung. As a result, previous investigation has focused on the development of in vivo animal models that are either genetically driven or antigen-induced. While these models capture some of the clinical and immunological features of human disease, most do not recapitulate extra-muscular manifestations such as interstitial lung disease. However, with recent advances in multi-omics technology, we now have the tools to better interrogate and define relevant disease pathways in existing disease models as well as human tissues—which should facilitate the development of novel therapeutic targets.
Given the current gaps in our understanding of IIM pathogenesis, there is a clear need to harness recent technological advances to develop more translational in vitro/in vivo disease models and to connect these disease models with in depth analyses of cells/tissues derived from humans with IIM. Key focus areas should include genetic risk factors, environmental triggers, and relevant cellular interactions that mediate the interface between innate and adaptive immunity. In particular, new research must examine the role of muscle satellite cells and differentiated myocytes as drivers of the aberrant immune response in diseased muscle. At the same time, we must better understand factors that govern the unique tissue tropism in different disease subsets of IIM, particularly the frequent involvement of both muscle and lung. Finally, we must elucidate the relative roles of antigen-driven humoral versus cellular immune responses in mediating damage to these tissues in order to guide future strategies for immunotherapeutic intervention. In view of these needs, we are soliciting original research and review articles that focus on (but are not limited to) the following areas:
• transcriptomic and computational analyses of human tissue-infiltrating cell populations
• in vivo/in vitro models of disease pathogenesis
• comparative immune profiling of muscle and extra-muscular organs
• role of innate vs adaptive immunity in mediating tissue phenotype
• muscle cells as drivers of immunopathology
• contributions of “non-immune” pathways to muscle dysfunction/weakness
Although IIM serves as a model of systemic autoimmunity, its relative rarity (estimated prevalence of 1 in 50,000) has complicated studies involving human cells/tissues. There is an extreme paucity of in vitro models capable of replicating many of the key cellular interactions that ultimately dictate immune infiltration of target tissues such as muscle and lung. As a result, previous investigation has focused on the development of in vivo animal models that are either genetically driven or antigen-induced. While these models capture some of the clinical and immunological features of human disease, most do not recapitulate extra-muscular manifestations such as interstitial lung disease. However, with recent advances in multi-omics technology, we now have the tools to better interrogate and define relevant disease pathways in existing disease models as well as human tissues—which should facilitate the development of novel therapeutic targets.
Given the current gaps in our understanding of IIM pathogenesis, there is a clear need to harness recent technological advances to develop more translational in vitro/in vivo disease models and to connect these disease models with in depth analyses of cells/tissues derived from humans with IIM. Key focus areas should include genetic risk factors, environmental triggers, and relevant cellular interactions that mediate the interface between innate and adaptive immunity. In particular, new research must examine the role of muscle satellite cells and differentiated myocytes as drivers of the aberrant immune response in diseased muscle. At the same time, we must better understand factors that govern the unique tissue tropism in different disease subsets of IIM, particularly the frequent involvement of both muscle and lung. Finally, we must elucidate the relative roles of antigen-driven humoral versus cellular immune responses in mediating damage to these tissues in order to guide future strategies for immunotherapeutic intervention. In view of these needs, we are soliciting original research and review articles that focus on (but are not limited to) the following areas:
• transcriptomic and computational analyses of human tissue-infiltrating cell populations
• in vivo/in vitro models of disease pathogenesis
• comparative immune profiling of muscle and extra-muscular organs
• role of innate vs adaptive immunity in mediating tissue phenotype
• muscle cells as drivers of immunopathology
• contributions of “non-immune” pathways to muscle dysfunction/weakness
Keywords: Idiopathic Inflammatory Myopathy (IIM), pathogenesis, disease models, multi-omics, innate immunity, adaptive immunity, therapy
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