The Microbiota and Epigenetic Regulation of T Helper 17/Regulatory T Cells: In Search of a Balanced Immune System

Abstract

Immune cells not only affect tissue homeostasis at the site of inflammation but also exert systemic effects contributing to multiple chronic conditions. Recent evidence clearly supports an altered T helper 17/regulatory T cell (Th17/Treg) balance leading to the development and progression of inflammatory diseases that not only affect the gastrointestinal tract but also have whole-body manifestations, including insulin resistance. Epigenetic mechanisms are amenable to both environmental and circulating factors and contribute to determining the T cell landscape. The recently identified participation of the gut microbiota in the remodeling of the epigenome of immune cells has triggered a paradigm shift in our understanding of the etiology of various inflammatory diseases and opened new paths toward therapeutic strategies. In this review, we provide an overview of the contribution of the Th17/Treg balance in the development and progression of inflammatory bowel diseases and metabolic diseases. We discuss the involvement of epigenetic mechanisms in the regulation of T cell function in the particular context of dysbiosis. Finally, we examine the potential for nutritional interventions affecting the gut microbiota to reshape the T cell epigenome and address the inflammatory component of various diseases.

Trace Amines and Their Receptors

“…i. Microbiota-Derived Trace Amines. There is a growing recognition of the role of the commensal microbiota in health and disease, including neurologic and psychiatric disorders (Dinan and Cryan, 2015;Fung et al, 2017), cancer and its chemotherapy (Alexander et al, 2017;Roy and Trinchieri, 2017), metabolic disorders (Sonnenburg and Bäckhed, 2016;Brunkwall and Orho-Melander, 2017), and immune disorders (Honda and Littman, 2016;Thaiss et al, 2016;Fung et al, 2017;Luo et al, 2017). Prokaryotes contain a large array of decarboxylase enzymes, many of which include L-amino acids in their substrate profile (Zheng et al, 2011;Nelson et al, 2015).…”

IL-33 and the intestine: The good, the bad, and the inflammatory

“…The balance between the canonically pro-inflammatory T H 17 cells and the anti-inflammatory T regulatory cells (Tregs) has been theorized to be an important regulator of inflammation in the gut during homeostasis and disease [99, 100]. This is particularly intriguing as both cell types are known to be enriched in the mucosal surface of the gut.…”

“…[103]. Interestingly, the composition of commensal bacterial that comprise the gut microbiome are postulated to play an important role in the balance of T H 17 and Tregs [99, 100]. The density of T H 17 cells in the gut is dependent on exposure to bacteria, as there is a relative paucity of T H 17 cells in mice raised in germ free conditions [106–109].…”

Psoriatic patients have a distinct structural and functional fecal microbiota compared with controls

“…Although relatively stable in adulthood, perturbations in the symbiosis existing between microbes and the human body have been implicated in the development of several immune‐mediated inflammatory diseases. In particular, gut dysbiosis has been linked to continuous immunological stimulation, resulting in systemic immune responses, which may include chronic inflammatory processes, such as psoriasis . Evidence for the role of the gut microbiome in psoriasis has been suggested by Zakostelska et al ., who have shown that exposure of mice to antibiotics inhibited psoriasis induction.…”

“…In particular, gut dysbiosis has been linked to continuous immunological stimulation, resulting in systemic immune responses, which may include chronic inflammatory processes, such as psoriasis. [3][4][5] Evidence for the role of the gut microbiome in psoriasis has been suggested by Zakostelska et al, 6 who have shown that exposure of mice to antibiotics inhibited psoriasis induction. The mice were characterized by an increase in fecal Lactobacilles, which suppress the interleukin-23-T-helper 17 axis, 7 implicated in psoriatic disease pathogenesis.…”