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.

Keywords: Alopecia Areata; diet; multiple sclerosis; systemic lupus erythematosus; therapeutic strategies; vitamin D.

Figure 1

The influence of distinct environmental factors on MS, AA and SLE. Environmental factors including Vitamin D, obesity, viral infections, hormones, microbiome, alcohol, diet, smoking and chemicals, have all been shown (with some extend of controversy) to interact with genes in patients with MS, SLE and AA.

Figure 2

Altered balance between pro-inflammatory and regulatory immune cells associated MS, SLE and AA. Increased frequencies of pro-inflammatory Th1/Th17 cells (IL-17+, IL-23+), effector B cells (IL-6+, TNF-α+, GM-CSF+), pro-inflammatory macrophage (GM-CSF+, IL-6+, IL-23+), and lack or dysfunctional anti-inflammatory regulatory T cells Tregs (IL-10+, IL-35+, TGFβ+), regulatory B cells Breg (IL-10+, IL-35+), anti-inflammatory plasmablasts (IL-10+) and anti-inflammatory macrophage (IL-13+, IL-10+ and TGF-β+). The altered balance between pro-inflammatory and regulatory profiles in MS, SLE and AA might be a result of an over activation of the immune system, or an insufficient regulation.