Abstract
The microbiome exerts considerable control over immune homeostasis and influences susceptibility to autoimmune and autoinflammatory disease (AD/AID) such as inflammatory bowel disease (IBD), multiple sclerosis (MS), type 1 diabetes (T1D), psoriasis, and uveitis. In part, this is due to direct effects of the microbiome on gastrointestinal (GI) physiology and nutrient transport, but also to indirect effects on immunoregulatory controls, including induction and stabilization of T regulatory cells (Treg). Secreted bacterial metabolites such as short-chain fatty acids (SCFA) are under intense investigation as mediators of these effects. In contrast, folate (vitamin B9), an essential micronutrient, has attracted less attention, possibly because it exerts global physiological effects which are difficult to differentiate from specific effects on the immune system. Here, we review the role of folate in AD/AID with some emphasis on sight-threatening autoimmune uveitis. Since folate is required for the generation and maintenance of Treg, we propose that one mechanism for microbiome-based control of AD/AID is via folate-dependent induction of GI tract Treg, particularly colonic Treg, via anergic T cells (Tan). Hence, folate supplementation has potential prophylactic and/or therapeutic benefit in AID/AD.
Highlights
Autoimmune diseases (AD) develop when there is breakdown of immunological tolerance to self-antigen in the adaptive immune system while autoinflammatory diseases (AID) occur when there are defects or dysregulation in the innate immune system [1]
In which experimental autoimmune uveitis (EAU) develops spontaneously due to lymphopenia and imbalance in [Teff :T regulatory cells (Treg)] ratio, we have shown that disease can be prevented by adoptive transfer of antigen-experienced Treg, but not by naïve Treg
The use of folate- and short-chain fatty acids (SCFA)-producing microbes has the potential to form the basis for a novel approach to prophylactic control of AD
Summary
Autoimmune diseases (AD) develop when there is breakdown of immunological tolerance to self-antigen in the adaptive immune system while autoinflammatory diseases (AID) occur when there are defects or dysregulation in the innate immune system [1] In both cases, a disordered microbiome has been implicated and, by inference, an altered bacterial flora including its secreted products [2]. A debilitating skin inflammation, and uveitis, a major sight-threatening disease in which infection may be a direct or indirect cause, are considered in many cases to be either an AD or an AID [7, 8]. In both AD and AID, there is failure of immune regulation (tolerance) and a disturbed microbiome. Circumstantial evidence for their role in AD and AID is the decline in Treg numbers in many of these conditions such as AS [10] as well as the effectiveness of adoptive Treg therapy in experimental models of AD and AID
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