Epigenetic Modulation as a Therapeutic Prospect for Treatment of Autoimmune Rheumatic Diseases

Abstract

Systemic inflammatory rheumatic diseases are considered as autoimmune diseases, meaning that the balance between recognition of pathogens and avoidance of self-attack is impaired and the immune system attacks and destroys its own healthy tissue. Treatment with conventional Disease Modifying Antirheumatic Drugs (DMARDs) and/or Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) is often associated with various adverse reactions due to unspecific and toxic properties of those drugs. Although biologic drugs have largely improved the outcome in many patients, such drugs still pose significant problems and fail to provide a solution to all patients. Therefore, development of more effective treatments and improvements in early diagnosis of rheumatic diseases are badly needed in order to increase patient's functioning and quality of life. The reversible nature of epigenetic mechanisms offers a new class of drugs that modulate the immune system and inflammation. In fact, epigenetic drugs are already in use in some types of cancer or cardiovascular diseases. Therefore, epigenetic-based therapeutics that control autoimmunity and chronic inflammatory process have broad implications for the pathogenesis, diagnosis, and management of rheumatic diseases. This review summarises the latest information about potential therapeutic application of epigenetic modification in targeting immune abnormalities and inflammation of rheumatic diseases.

Microbiome, inflammation, epigenetic alterations, and mental diseases

“…In the IL‐23/IL‐17 pathway, IL‐23 increases the excretion of the pro‐inflammatory cytokine IL‐17, which in turn enhances the production of pro‐inflammatory mediators such as IL‐1β, IL‐6, IL‐8, and TNF‐α (Andrews et al, ). These molecules are produced by immune cells under chronic inflammatory conditions (Figure ), which consequently lead to the development of many diseases such as UC, CD, and autoimmune disorders (Ciechomska & O'Reilly, ). Furthermore, recent studies have provided evidence that the imbalance of specific bacterial species in human gut contributes to IBD, CD, and UC pathogenesis through inflammatory processes which in part could be remedied by antibiotic therapy (Lopez‐Siles et al, ; Mirsepasi‐Lauridsen et al, ; Zhou et al, ).…”

Toll Like Receptors in systemic sclerosis: An emerging target

“…Negative regulation of TLR activation is important to restrain inappropriate inflammation and this occurs through microRNAs. MicroRNAs are epigenetic regulators of gene expression by negatively regulating gene expression by binding to the 3'UTR of target mRNAs [10]. One of the most inducible microRNAs after LPS stimulation is microRNA155 that elevates to negatively regulate the immune response by targeting SHIP1 [11].…”

The Bromodomain and Extra-Terminal Protein Inhibitor OTX015 Suppresses T Helper Cell Proliferation and Differentiation

“…Epigenetic modulation empowers the differential expression of lineage-specific signature genes in T cells to dictate T cell fate and function and regulate the immune system [5]. Consequently, therapeutics targeting epigenetic proteins are being developed to fine-tune the immune response with a view to clinical application in the treatment of autoimmune disorders [6,7].…”