Immunoepigenetic Regulation of Inflammatory Bowel Disease: Current Insights into Novel Epigenetic Modulations of the Systemic Immune Response

Abstract

The immune system and environmental factors are involved in various diseases, such as inflammatory bowel disease (IBD), through their effect on genetics, which modulates immune cells. IBD encompasses two main phenotypes, Crohn’s disease, and ulcerative colitis, which are manifested as chronic and systemic relapse-remitting gastrointestinal tract disorders with rising global incidence and prevalence. The pathophysiology of IBD is complex and not fully understood. Epigenetic research has resulted in valuable information for unraveling the etiology of this immune-mediated disease. Thus, the main objective of the present review is to summarize the current findings on the role of epigenetic mechanisms in IBD to shed light on their potential clinical relevance. This review focuses on the latest evidence regarding peripheral blood mononuclear cells and epigenetic changes in histone modification, DNA methylation, and telomere shortening in IBD. The various identified epigenetic DNA profiles with clinical value in IBD could be used as biomarkers for more accurately predicting disease development, treatment response, and therapy-related adverse events. Ultimately, the information presented here could be of potential relevance for future clinical practice in developing more efficient and precise medicine to improve the quality of life for patients with IBD.

Identification and immunological characterization of cuproptosis-related molecular clusters in ulcerative colitis

“…UC is a common disease of the immune-mediated digestive system. The immune system influenced the disease development by modulating the infiltration of immune cells in the diseased area [ 36 ]. T cell immunotherapy had an outstanding advantage in the treatment of ulcerative colitis [ 37 ].…”

MicroRNA and granulocyte‐monocyte adsorption apheresis combotherapy after inadequate response to anti‐TNF agents in ulcerative colitis

“…5 Both tissue-derived, circulating, and fecal microRNAs have been explored as promising biomarkers in the diagnosis and the prognosis of the disease severity of IBD. 6 In addition to the potential role as diagnostic biomarkers, miRNAs in IBD are also interesting tools for potential biomarkers to response in the biologic therapies. Current biological therapies are directed against inflammatory mediators involved within the pathophysiology of IBD and have revolutionized medical treatment: anti-TNF therapy (eg, infliximab, golimumab, adalimumab), monoclonal antibodies (eg, the anti-alpha4beta7 integrin inhibitor vedolizumab and the anti-IL12/23p40 antibody ustekinumab), newer target therapies (the JAK-inhibitors as tofacitinib, upadacitinib and filgotinib, and the sphingosine-1-phosphate receptor modulator ozanimod).…”

“…It is well‐established that miRNAs modulate inflammatory cascades and affect the extracellular matrix, tight junctions, cellular hemostasis, and microbiota 5 . Both tissue‐derived, circulating, and fecal microRNAs have been explored as promising biomarkers in the diagnosis and the prognosis of the disease severity of IBD 6 . In addition to the potential role as diagnostic biomarkers, miRNAs in IBD are also interesting tools for potential biomarkers to response in the biologic therapies.…”

“…In research, the use of peripheral blood as a source of samples to identify and study the microRNA profiles of IBD still offers many advantages to other samples, such as colon tissues, which require the invasive procedure of colonoscopy. 1,6 Among the therapeutic options for UC, the nonpharmacological treatment strategy with granulocyte and monocyte apheresis (GMA) with Adacolumn (JIMRO Co, Japan) has been applied to induce remission in patients with active UC. 7,8 GMA is an extracorporeal vein-to-vein technique, filled with cellulose acetate beads to interact with fragment crystallizable-gamma receptor (FcγR) expressed at the surface of activated leukocytes.…”

“…MiRNAs play an important biological role as regulators of cell function and homeostasis, so their impaired activities are linked to disease, as is the case for UC. In research, the use of peripheral blood as a source of samples to identify and study the microRNA profiles of IBD still offers many advantages to other samples, such as colon tissues, which require the invasive procedure of colonoscopy 1,6 …”