Differential impact of environmental factors on systemic and localized autoimmunity

Abstract

The influence of environmental factors on the development of autoimmune disease is being broadly investigated to better understand the multifactorial nature of autoimmune pathogenesis and to identify potential areas of intervention. Areas of particular interest include the influence of lifestyle, nutrition, and vitamin deficiencies on autoimmunity and chronic inflammation. In this review, we discuss how particular lifestyles and dietary patterns may contribute to or modulate autoimmunity. We explored this concept through a spectrum of several autoimmune diseases including Multiple Sclerosis (MS), Systemic Lupus Erythematosus (SLE) and Alopecia Areata (AA) affecting the central nervous system, whole body, and the hair follicles, respectively. A clear commonality between the autoimmune conditions of interest here is low Vitamin D, a well-researched hormone in the context of autoimmunity with pleiotropic immunomodulatory and anti-inflammatory effects. While low levels are often correlated with disease activity and progression in MS and AA, the relationship is less clear in SLE. Despite strong associations with autoimmunity, we lack conclusive evidence which elucidates its role in contributing to pathogenesis or simply as a result of chronic inflammation. In a similar vein, other vitamins impacting the development and course of these diseases are explored in this review, and overall diet and lifestyle. Recent work exploring the effects of dietary interventions on MS showed that a balanced diet was linked to improvement in clinical parameters, comorbid conditions, and overall quality of life for patients. In patients with MS, SLE and AA, certain diets and supplements are linked to lower incidence and improved symptoms. Conversely, obesity during adolescence was linked with higher incidence of MS while in SLE it was associated with organ damage. Autoimmunity is thought to emerge from the complex interplay between environmental factors and genetic background. Although the scope of this review focuses on environmental factors, it is imperative to elaborate the interaction between genetic susceptibility and environment due to the multifactorial origin of these disease. Here, we offer a comprehensive review about the influence of recent environmental and lifestyle factors on these autoimmune diseases and potential translation into therapeutic interventions.

The role of vitamin D in pediatric systemic lupus erythematosus - a double pawn in the immune and microbial balance

“…The food components and the method of preparation regulate the balance of the internal environment, intestinal transit and absorption, thereby modulating the risk of atopy, autoimmunity and Bacteroidetes-Firmicutes/Proteobacteria balance. Functionally, vitamin A, B9, short-chain fatty acids and omega 3 fatty acids have anti-inflammatory, antioxidant and cardioprotective effects, while omega 6 and 9 fatty acids appear to improve intestinal cell junctions ( 64 , 65 , 68 – 72 ). The implication of caloric restriction and intermittent fasting is another research topic.…”

“…The implication of caloric restriction and intermittent fasting is another research topic. Unlike fasting, where beneficial effects have not been identified, caloric restriction seems to positively influence SLE morbidity and mortality ( 31 , 64 , 73 – 75 ).…”

“…The possible mechanisms of action are the modulation of the expression of chemokine receptors in dendritic cells and the decrease of Th17 lymphocytes, IL-17, Toll-like receptors (TLR) -4, TLR-5, TLR-7 and TLR-9, together with the favoring of regulatory T cells. However, the administration of Lactobacillus can also be harmful, depending on the environmental and individual characteristics of the patient ( 63 , 64 , 84 – 88 ). The SLE activity estimated by the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) activity score seems to be correlated with the variable abundance of fecal and salivary bacteria.…”

“…Due to the multiple roles, it plays in the body, starting from the regulation of chronic inflammation (cytokines and inflammatory markers), anti-inflammatory effects, directing the maturation and regulation of immune cells, decreasing the production of antibodies and oxidative stress, but also marking the risk of cardiovascular events, B vitamins (B1, B2, B6, B9, B12) and vitamins E, C and A play a major role in dictating the biological changes of any SLE patient. Thus, the priority of supplementation is emphasized when they are in deficit ( 64 ). Regarding the markers that can be dosed in order to evaluate the nutritional status and the cardiovascular risk, Salomão RG.…”

“…The electrolytes are also necessary to be evaluated, since sodium and potassium compete to modulate the Th17/T regulatory balance, inflammation, the level of anti-dsDNA antibodies and the complement fractions (C3 and C4) and consequently the individualization of the diet according to them may have benefits on symptom control ( 64 ). Along with these, other essential trace elements (iron, copper, zinc, selenium) have proven their necessity in the differentiation, activation and functioning of immune cells.…”