Immune-mediated disease caused by climate change-associated environmental hazards: mitigation and adaptation

Abstract

Global warming and climate change have increased the pollen burden and the frequency and intensity of wildfires, sand and dust storms, thunderstorms, and heatwaves - with concomitant increases in air pollution, heat stress, and flooding. These environmental stressors alter the human exposome and trigger complex immune responses. In parallel, pollutants, allergens, and other environmental factors increase the risks of skin and mucosal barrier disruption and microbial dysbiosis, while a loss of biodiversity and reduced exposure to microbial diversity impairs tolerogenic immune development. The resulting immune dysregulation is contributing to an increase in immune-mediated diseases such as asthma and other allergic diseases, autoimmune diseases, and cancer. It is now abundantly clear that multi-sectoral, multidisciplinary, and transborder efforts based on Planetary Health and One Health approaches (which consider the dependence of human health on the environment and natural ecosystems) are urgently needed to adapt to and mitigate the effects of climate change. Key actions include reducing emissions and improving air quality (through reduced fossil fuel use), providing safe housing (e.g., improving weatherization), improving diets (i.e., quality and diversity) and agricultural practices, and increasing environmental biodiversity and green spaces. There is also a pressing need for collaborative, multidisciplinary research to better understand the pathophysiology of immune diseases in the context of climate change. New data science techniques, biomarkers, and economic models should be used to measure the impact of climate change on immune health and disease, to inform mitigation and adaptation efforts, and to evaluate their effectiveness. Justice, equity, diversity, and inclusion (JEDI) considerations should be integral to these efforts to address disparities in the impact of climate change.

Keywords: Air pollution; allergy; asthma; biodiversity; climate change; immune diseases; mitigation; pollen.

Figure 1.

Effects of climate change-related events on immune dysregulation and human health through immune-mediated conditions. Climate change increases the frequency and severity of various types of events that affect the human exposome (the totality of a person’s lifetime exposures). The resulting immune dysregulation can cause a variety of immune-mediated conditions such as allergies, asthma, autoimmune diseases, and cancers. These risks are increased by susceptibility factors in individuals and within vulnerable populations.

Figure 2.

Climate-change-associated exposures, such as pollen, air pollutants, and heat stress, trigger complex pathways mediating both inflammatory and tolerogenic responses. Penetration of allergens, pollutants, and other environmental stressors via a defective epithelial barrier leads to the release of pro-inflammatory cytokines such as interleukin (IL)-25, IL-33, and thymic stromal lymphopoietin (TSLP) and the skewing of T helper (Th) naïve cells to Th2 cells. Th2 cells mediate a proinflammatory cascade through cytokines IL-4, IL-5, IL-9, and IL-13, leading to a B cell isotype class switching to immunoglobulin (Ig)E. IgE bound to mast cells and basophils cross-link on subsequent allergen exposure, leading to the release of pro-inflammatory mediators such as histamine and prostaglandins. In allergies, these lead to enhanced vascular permeability, smooth muscle contraction, and eosinophilic infiltration, resulting in symptoms of bronchoconstriction. Heat stress and air pollutants work synergistically to mediate these proinflammatory effects. The immune system also actively mediates tolerogenic effects to commonplace environmental agents. Here, naïve Th cells are transformed into regulatory T cells (Tregs) which favor B cell isotype class switching to anti-inflammatory IgA and IgG4.

Figure 3.

Climate change effects on pollen. (A) Global warming is causing longer growing seasons, which in turn leads to longer allergy seasons that start earlier in spring and last later into autumn. The figure shows data from 201 cities in the United States, plotting the number of days between the annual last and first occurrence of a temperature of 0°C (32°F), i.e., the first and last freezes of the year, over time—indicating a lengthening of the growing season. Adapted from Climate Central with permission (220). (B) Pollen concentrations increase with increases in atmospheric carbon dioxide (CO₂). Figure shows pollen production in common ragweed grown at pre-industrial CO₂ concentrations (280 ppm), current concentrations (370 ppm) and a projected 21st century concentration (600 ppm). Error bars indicate the standard error. The Student–Newman–Keuls test was used to determine differences among the CO₂ treatments at the 0.05 significance level. Adapted from Ziska, et al. (221) with permission from CSIRO Publishing.

Figure 4.

Contribution of air pollution to mortality rates globally. (A) Percentage of the population in 2017 exposed to mean annual ambient outdoor concentrations of particulate matter (PM_2.5) that exceed 10 µg/m³/year, the guideline value recommended by the World Health Organization as the lower end of the range of concentrations over which adverse health effects due to PM_2.5 exposure have been observed (70). (B). Percentage of deaths in 2019, from any cause, attributed to outdoor air pollution (from ambient particulate matter and ozone) as a risk factor (70). (C) Age-standardized death rates from outdoor air pollution (number of deaths per 100,000 individuals) in 1990 and 2019 (70).

Figure 5.

Percentage of deaths in 2019, from any cause, attributed to indoor air pollution (from burning solid fuels) as a risk factor (102).

Figure 6.

Mitigation and adaption actions to address increases in immune-mediated diseases associated with the exposome effects of climate change.