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Regulation of Innate Inflammatory Responses

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Damage-Associated Molecular Patterns in Human Diseases

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Abstract

This chapter addressed one of the most important issues of inflammatory innate immune effector responses: mechanisms of their regulation aimed at avoiding auto-destructive “suicidal” pathologies caused by uncontrolled exaggerated DAMP-induced inflammatory pathways. From the various evolutionarily developed regulatory mechanisms described in the literature, here, three essential regulatory mechanisms are briefly highlighted: epigenetic reprogramming, post-translational modifications, and metabolic changes. Regulating epigenetic changes can be categorized into several major biochemical mechanisms, including changes in (1) DNA methylation; (2) covalent histone post-translational modifications such as histone acetylation, methylation, phosphorylation, and ubiquitination; and (3) RNA-based mechanisms as mediated by small and long non-coding RNAs. Such chromatin modifiers were shown to execute coordinated actions to convert extracellular stimuli into the complex gene expression patterns during innate inflammatory responses. As a striking example of epigenetic regulation, the phenomenon of “trained immunity” is briefly touched reflecting the fact that the innate immune system—like the adaptive immune system—possesses a memory as well. In addition, evidence is presented for a role of post-translational modifications such as phosphorylation, methylation, or acetylation in influencing PRM-dependent inflammatory responses via targeting of innate sensors and downstream signalling molecules, including receptors, adaptors, enzymes, and transcriptional factors. Finally, in this chapter, some remarks are made regarding profound changes in intracellular metabolic pathways in innate immune cells such as dendritic cells and macrophages that alter their function when getting activated to execute effector responses. As a typical metabolic modification, the shift from mitochondrial oxidative phosphorylation in resting innate immune cells to aerobic glycolysis in activated cells is particularly mentioned.

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  1. University of Strasbourg, Molecular ImmunoRheumatology, Laboratory of Excellence Transplantex, Strasbourg, France

    Walter Gottlieb Land

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Land, W.G. (2018). Regulation of Innate Inflammatory Responses. In: Damage-Associated Molecular Patterns in Human Diseases. Springer, Cham. https://doi.org/10.1007/978-3-319-78655-1_24

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  • DOI: https://doi.org/10.1007/978-3-319-78655-1_24

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