About this Research Topic
Post-translational modifications (PTMs) regulate protein structure, localization, activity and immunogenicity. PTMs of immune sensors, mediators, signaling molecules and antigens exert profound influences on all aspects of immunity. There is also accumulating evidence that protein PTMs are involved in the pathogenesis of immune-mediated diseases.
PTMs are intensively studied in the context of intracellular signal transduction that heavily relies on the orchestrated relay of phosphorylation and ubiquitination events, amongst others. These allow subsequent activation of key enzymes, recruitment of downstream adaptor proteins or degradation of inhibitor molecules. Consequently, the therapeutic value of chemical compounds or biologics targeting the activity of specific enzymes responsible for these PTMs is evaluated in clinical trials for a variety of pathologies, including autoimmune and inflammatory disorders.
However, the role of PTMs is not limited to intracellular signaling, and extends to the regulation of proteins with extracellular activity. Irreversible or stress-induced PTMs such as proteolysis, ROS-induced oxidative changes, carbamylation, or citrullination, which often occur at sites of inflammation, affect both host defense and immunopathology. For example, proteolytic maturation of IL-1 family members by extracellular proteases, derived from infiltrating immune cells or from invading pathogens or allergens, amplifies inflammatory responses. PTMs of chemokines and antimicrobial peptides change their immune-modulatory and antimicrobial functions, and PTMs of self-antigens are involved in the pathogenesis of several autoimmune diseases.
The goal of this Research Topic is to collate and highlight current research, discussions and opinions pertaining to this fascinating subject, and to provide an overview of the immunoregulatory PTMs of extracellular mediators, such as cytokines, chemokines, or antigens in the context of chronic inflammatory or autoimmune diseases.
In this Research Topic, we welcome the submission of Original Research, Review, Systematic Review, Mini Review, and Methods articles pertaining to the role of post-translational protein modifications in inflammatory and immune responses that cover, but are not limited to, the following topics:
1. PTMs regulating the activity of extracellular immune mediators, such as cytokines or chemokines, and their role in the pathogenesis of chronic inflammatory diseases or autoimmune diseases
2. Irreversible or stress-induced PTMs of immune mediators and their role in inflammation, immune responses and host defense
3. PTMs of antigens and their role in the pathogenesis of autoimmune diseases
4. The potential of PTMs and protein modifying enzymes as therapeutic targets in immune-mediated diseases
Keywords: post-translational modifications, autoantigens, cytokines, chemokines, inflammation, chronic inflammatory diseases, extracellular signaling
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