Allergy Asthma Immunol Res.  2014 Sep;6(5):389-400. 10.4168/aair.2014.6.5.389.

Environmental Changes, Microbiota, and Allergic Diseases

• Kim BJ
• Lee SY
• Kim HB
• Lee E
• Hong SJ

• KMID: 2181074
• DOI: http://doi.org/10.4168/aair.2014.6.5.389

Abstract

During the last few decades, the prevalence of allergic disease has increased dramatically. The development of allergic diseases has been attributed to complex interactions between environmental factors and genetic factors. Of the many possible environmental factors, most research has focused on the most commonly encountered environmental factors, such as air pollution and environmental microbiota in combination with climate change. There is increasing evidence that such environmental factors play a critical role in the regulation of the immune response that is associated with allergic diseases, especially in genetically susceptible individuals. This review deals with not only these environmental factors and genetic factors but also their interactions in the development of allergic diseases. It will also emphasize the need for early interventions that can prevent the development of allergic diseases in susceptible populations and how these interventions can be identified.

Keyword

Allergic disease; climate change; epigenetics; gene-environmental interaction; microbiota; pollution

MeSH Terms

Air Pollution
Climate Change
Early Intervention (Education)
Epigenomics
Microbiota*
Prevalence

Figure

• 

  Fig. 1 Microflora hypothesis. Environmental changes influence the development of NCDs, including allergic diseases, by decreasing the environmental and human microbiota diversity during crucial periods of life, which induces immune dysregulation. NCDs, Noncommunicable diseases.

• 

  Fig. 2 Mechanisms of airway injury by air pollutants that induce oxidative stress and overpower the antioxidant system in the airway. DEPs, diesel exhaust particles; GSH, glutathione; NO2, nitrogen dioxide; O3, ozone; PM, particulate matter.

• 

  Fig. 3 Epigenetic mechanisms in allergic diseases. (A) DNA methylation. After birth, CD4+ T cells undergo progressive demethylation (white circle) in the IFN-γ promoter, which increases their expression of IFN-γ which is the master cytokine of Th1 responses. Concomitant de novo methylation (black circle) of IL-4 and IL-13 loci represses the expression of these cytokines, which are responsible for allergic responses. Therefore, a Th2 skewed response at birth is balanced by an increased response toward Th1. However, when the IL-4 gene promoter undergoes demethylation, GATA3 (a master transcription factor of Th2) can bind the GATA3-binding site of the IL-4 promoter and thereby increase IL-4 production. This induces the synthesis of IL-5 and IL-13 and the methylation of the IFN-γ promoter, which skews the immune system towards Th2 responses. (B) Histone modification. Signal transducer and activator of transcription (STAT) proteins transmit cytokine-mediated signals and initiate transcription, thereby specifying Th-cell differentiation. The activation of STAT4 allows histone acetlyation (black triangle) at the IFN-γ promoter, which facilitate STAT4 binding and thereby increases IFN-γ production.

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  Fig. 4 Multiple interactions between air pollution, genetic polymorphism, and epigenetic markers. The NOS2A gene, which encodes inducible nitric oxide synthase, is known to modify the effect of air pollution on airway inflammation. NOS2A promoter haplotypes significantly influenced adjacent DNA methylation and high PM2.5 exposure associates with lower NOS2A methylation. These NOS2A genetic and epigenetic variations together with exposure to high levels of PM2.5 synergistically affect the levels of FeNO, which is an in-vivo airway inflammatory marker. FeNO, fractional exhaled nitric oxide; iNOS, inducible nitric oxide synthase; NOS2A, nitric oxide synthase 2A; PM, particulate matter.

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