Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2019 Apr 1;129(4):1504-1515.
doi: 10.1172/JCI124612. Epub 2019 Feb 11.

Environmental exposures and mechanisms in allergy and asthma development

Liza Bronner Murrison  1   2 , Eric B Brandt  1 , Jocelyn Biagini Myers  1   2 , Gurjit K Khurana Hershey  1   2
Affiliations
Review

Environmental exposures and mechanisms in allergy and asthma development

Liza Bronner Murrison et al. J Clin Invest. .

Abstract

Environmental exposures interplay with human host factors to promote the development and progression of allergic diseases. The worldwide prevalence of allergic disease is rising as a result of complex gene-environment interactions that shape the immune system and host response. Research shows an association between the rise of allergic diseases and increasingly modern Westernized lifestyles, which are characterized by increased urbanization, time spent indoors, and antibiotic usage. These environmental changes result in increased exposure to air and traffic pollution, fungi, infectious agents, tobacco smoke, and other early-life and lifelong risk factors for the development and exacerbation of asthma and allergic diseases. It is increasingly recognized that the timing, load, and route of allergen exposure affect allergic disease phenotypes and development. Still, our ability to prevent allergic diseases is hindered by gaps in understanding of the underlying mechanisms and interaction of environmental, viral, and allergen exposures with immune pathways that impact disease development. This Review highlights epidemiologic and mechanistic evidence linking environmental exposures to the development and exacerbation of allergic airway responses.

PubMed Disclaimer

Conflict of interest statement

Conflict of interest: The authors have declared that no conflict of interest exists.

Figures

Figure 1
Figure 1. Epithelial pathways impacted by environmental exposures promote asthma pathogenesis.
Exposure to air pollutants induces oxidative stress. AhR recognizes polycyclic aromatic hydrocarbons on diesel exhaust particles (DEPs), promoting cytochrome P450 family 1 A1–mediated (CYP1A1-mediated) detoxification. Oxidative stress induces Nrf2 translocation to the nucleus, leading to antioxidant transcription. Failure to detoxify results in release of the neutrophil chemokine IL-8, the antigen-presenting cell (APC) chemokine CCL20, and proinflammatory cytokines (including IL-1, IL-6, and TNF-α) that in the absence of allergen promote naive T cell differentiation into IL-17A–producing Th17 cells. Similarly, exposure to mold-derived β-glucans, which signal through dectin-1, induces recruitment of IL-17A–secreting Th17 and γδT cells and neutrophils. Mold and other complex allergens also stimulate epithelial cells through pathogen-associated molecular pattern (PAMP) receptors like TLRs. TLR4 recognizes the house dust mite allergen Derp2 and endotoxins, which can modulate NF-κB activation of proinflammatory cytokines via the ubiquitin-modifying enzyme A20. Notch4-Jagged1 interaction between T cells and APCs, respectively, can induce Th2 cell generation when APCs are exposed to allergens and epithelial cell–derived IL-25, IL-33, and/or TSLP. These cytokines can be released following viral infection of epithelial cells and cellular damage resulting from exposure to pollutants and/or proteolytic allergens. They can induce innate lymphoid cells (ILC2s) to release IL-13, which drives mucus production and AHR, and IL-5, which is central to eosinophil biology. In addition to interacting with APCs and Th2 cells to potentiate allergic responses and IgE generation, ILC2s also release amphiregulin (AREG) to promote tissue repair. HRV and RSV infections in asthmatics can exacerbate Th2 responses and inhibit type 1 IFN responses, enhancing viral replication and promoting more severe disease.
Figure 2
Figure 2. Interplay of indoor and outdoor environmental exposures and host factors that affect lifelong allergic disease development and progression.
Allergic disease development is influenced by many environmental exposures that may interact with host factors and trigger a host response. These exposures may be part of the outdoor, indoor, or host environment. The timing of environmental exposures is important in the development and progression of allergic disease. Common factors within the external, internal, and host environments contribute to disease development, exacerbation, and lifelong progression. The host response to different exposures varies depending on host genetics and epigenetics in addition to other host factors that influence the timing and onset of allergic disease symptoms and severity.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Burbank AJ, Sood AK, Kesic MJ, Peden DB, Hernandez ML. Environmental determinants of allergy and asthma in early life. J Allergy Clin Immunol. 2017;140(1):1–12. doi: 10.1016/j.jaci.2017.05.010. - DOI - PMC - PubMed
    1. Kanchongkittiphon W, Mendell MJ, Gaffin JM, Wang G, Phipatanakul W. Indoor environmental exposures and exacerbation of asthma: an update to the 2000 review by the Institute of Medicine. Environ Health Perspect. 2015;123(1):6–20. doi: 10.1289/ehp.1307922. - DOI - PMC - PubMed
    1. Butsch Kovacic M, et al. The Greater Cincinnati Pediatric Clinic Repository: a novel framework for childhood asthma and allergy research. Pediatr Allergy Immunol Pulmonol. 2012;25(2):104–113. doi: 10.1089/ped.2011.0116. - DOI - PMC - PubMed
    1. Kay AB. Allergy and allergic diseases. First of two parts. N Engl J Med. 2001;344(1):30–37. doi: 10.1056/NEJM200101043440106. - DOI - PubMed
    1. Bantz SK, Zhu Z, Zheng T. The atopic march: progression from atopic dermatitis to allergic rhinitis and asthma. J Clin Cell Immunol. 2014;5(2):202. - PMC - PubMed

Publication types