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Increased anthropogenic activity, including deforestation, urbanization, modern agricultural practices, manufacture of synthetic chemicals, overuse of fertilizers and antibiotics, and the use of fossil fuels and biomass for energy, have altered Earth’s environment. Global temperatures and the frequency and severity of climate change events such as heatwaves, wildfires, sand and dust storms (SDSs), and thunderstorms have all increased over recent decades (1). These events further increase global warming. For example, wildfires release large amounts of greenhouse gases (GHGs) further contributing to air pollution and global warming, and accelerating the vicious climate feedback loop. Climate change events lead to increases in pollen burden, air pollution, flooding, and heat stress, which physically, chemically, and biologically alter the human exposome (i.e., the cumulative environmental exposures encountered by an individual in a lifetime). Wider environmental determinants of health are also affected by climate change, including biodiversity loss and access to nutritious food, clean drinking water, and secure shelter ( Figure 1 ).

Humans have evolved an immune system to protect against environmental assaults and maintain health. The epithelial barriers of the gut, lungs, and skin are the body’s first line of defense. Immune cells within the epithelial layer determine the extent of the threat posed by foreign invaders and mount a response. However, overreaction and hypersensitivity of the immune system leads to immune dysregulation, which can result in allergic diseases, autoimmune diseases, and cancer—conditions whose prevalence rates have increased in recent decades (2–4). In recent decades, increased urbanization, antibiotic use, and exposure to toxic chemicals—coupled with decreased exposure to biodiverse environments, less diverse diets, and a lack of physical activity—have created conditions that increase the risks of skin and mucosal barrier disruption, microbial dysbiosis, and immune dysregulation in populations globally (5). The epithelial barrier hypothesis proposes that increases in exposure to air pollutants and other toxic substances in the air, water, and foodstuffs (such as detergents, household cleaners, food emulsifiers, preservatives, pesticides, and microplastics) damage the epithelial barrier. This damage increases the penetration of allergens and microbes, leading to increases in pro-inflammatory reactions (6). A defective epithelial barrier has been demonstrated in asthma and allergic diseases (7). In addition, gut barrier defects and microbial dysbiosis have been demonstrated in many allergic and autoimmune diseases and cancers (8, 9). In parallel, a loss of biodiversity and limited exposure to microbial diversity increasingly impair tolerogenic immune development.

Major allergic diseases include allergic asthma, allergic rhinitis, atopic dermatitis, and food allergy. The estimated prevalence of allergies varies by age group, allergy type, geographical region, and season, and has changed over time. Methodological differences between studies can explain some of the observed variance in rates. However, the consensus is that, overall, there has been an upward trend in the prevalence of asthma and allergies (10–14). These diseases have a serious impact on individuals’ quality of life and incur substantial direct healthcare costs and indirect socioeconomic costs (15). Based on Global Cancer Observatory (GLOBOCAN) and World Health Organization (WHO) sources, cancer is a leading and increasing cause of mortality and morbidity worldwide. Globally, cancer caused approximately 10 million deaths in 2020, and it is the first or second leading cause of death in many countries (16, 17). The incidence of cancer in adults aged 50 years or younger has increased worldwide since the 1900s (18) and cancer risk has been linked to environmental factors such as air pollution (19, 20). Autoimmune diseases include rheumatoid arthritis, systemic lupus erythematosus, inflammatory bowel diseases (such as ulcerative colitis and Crohn’s disease), and multiple sclerosis. The overall prevalence of autoimmunity is estimated to be approximately 3–5% in the general population. The incidence and prevalence of autoimmune diseases vary with age, gender, and ethnicity, with women being more at risk than men (21). These diverse conditions also incur a vast and rising disease burden globally (22) and accumulating evidence links their incidence to pollution (23).

Without mitigation of the environmental risk factors driven by climate change, further increases in allergic diseases, autoimmune diseases, and cancers are expected (24, 25). Global temperatures are 1.1°C higher than during prehistorical times and future global warming is projected to span a range from 1.4°C to 4.4°C by 2100, depending on different GHG emissions scenarios (26). The magnitude of the increase depends on the extent of human interventions aiming at (i) the reduction of fossil fuel use; (ii) the implementation of eco-friendly sustainable practices; and (iii) enforcing equitable socioeconomic factors. With the recognition of the imminent threats to health and the need for global cooperation, the 2015 Paris Agreement signed at the United Nations Climate Conference (COP) 21 aims to limit global warming to well below 2°C and as close to 1.5°C as possible by promoting transitions toward low-emission and climate-resilient development (27). Nevertheless, even an optimistic projected global temperature increase of 1.5°C will have major consequences for human health, including immune-mediated diseases. Many studies have shown that the adverse effects of climate change on disease risk are higher among those of a lower socioeconomic status, those of younger or older age, and those with comorbid diseases such as cardiovascular diseases, asthma, or other atopic diseases (28).

In this article, we review the links between climate change, environmental exposures, and immune dysregulation and its associated diseases. We then recommend adaptation and mitigation solutions to reduce the impact of climate change on human health via these conditions.

Climate change-associated exposures can trigger a complex array of inflammatory or tolerogenic responses ( Figure 2 ). In healthy individuals, the immune system mediates a tolerogenic response upon encountering common innocuous environmental factors. During immune dysregulation, the immune system mounts an inflammatory response, even to innocuous environmental factors or healthy cells in the body. The mechanisms involved in allergic reactions to pollen, food, or insect allergens are those best understood.

A defective epithelial barrier permits the entry of allergens, leading to the release of pro-inflammatory epithelium-derived cytokines such as interleukin (IL)-25, IL-33, and thymic stromal lymphopoietin (TSLP). These cytokines further prompt dendritic cells to transform naïve T helper (Th) cells into Th2 cells, which release pro-inflammatory cytokines such as IL-4, IL-5, IL-9, and IL-13. Epithelial cytokines also activate type 2 innate lymphoid cells (ILC2s) which also release pro-inflammatory cytokines IL-5 and IL-13. These cytokines favor B cell class switching to immunoglobulin (Ig)E. Allergic sensitization occurs when IgE binds to the high-affinity IgE receptor FcϵR1 on mast cells. In these individuals, subsequent exposure to allergens favors IgE cross-links and the release of preformed and de novo–synthesized pro-inflammatory mediators, such as histamine, prostaglandins, leukotrienes, and other cytokines. In allergies, these proinflammatory mediators enhance vascular permeability, smooth muscle contraction, and eosinophilic infiltration, resulting in symptoms of bronchoconstriction.

The immune system also mediates tolerogenic mechanisms. Here, naïve Th cells are transformed into tolerogenic regulatory T cells (Tregs) rather than inflammatory Th2 cells. Tregs favor B cell isotype class switching to IgA and IgG4, both of which block Th2 inflammatory responses (29). The environmental factors hypothesized to increase the likelihood of inflammatory rather than tolerogenic responses include microbial and epithelial barrier dysregulation, increased hygiene, early life avoidance of allergens, refined diet, and air pollution (30).

Changes in land use and climate, such as rising temperatures and nitrogen oxides (NOx), ozone (O₃), and carbon dioxide (CO₂) levels, have led to increased pollen quantity, quality, allergenicity, and duration of the pollen season ( Table 1 , Figure 3 ) (38, 41). In one study, the production of allergenic pollen by ragweed increased by 61% when CO₂ concentrations were doubled (42). Greenhouse and field studies indicate that pollen concentrations are correlated with temperature and some estimates suggest that pollen concentrations may increase by 200% by the end of the century (37). Most pollen types have shifted toward earlier times of the year for pollen outputs (e.g., ragweed), possibly aggravating the burden on pollen-allergic patients (37, 38). Nitrogen dioxide (NO₂) and O₃ have also been shown to damage Platanus pollen cell membranes, increase the concentration of the Platanus pollen allergen a 3 released into the atmosphere, and alter its protein structure via nitrification and oxidation—enhancing its immunogenicity and stability (43).

The intensification of pollen exposure has important implications for public health. Increased allergenicity of pollen results in more severe symptoms in allergic individuals (32). There is increasing evidence correlating high pollen levels (especially grass pollen) with higher rates of asthma exacerbations and associated emergency department visits and hospitalization (44–46).

Furthermore, pollen is also affected by thunderstorms, leading to a phenomenon called thunderstorm asthma (TA) characterized by severe asthma attacks and asthma-related deaths in patients with allergic rhinitis. First described nearly 40 years ago, TA has been reported in North America, Europe, the Middle East, and Australia. TA events result from a complex interaction of environmental and individual susceptibility factors (47). Environmental factors include high concentrations of an aeroallergen and rain and moisture that rupture pollen grains and fungal spores, leading to the release of fine allergen-bearing starch granules that are <2.5 µm in size (48). Individual susceptibility factors include (i) pre-sensitization to seasonal aeroallergens; (ii) history of seasonal allergic rhinitis; and (iii) low rates of inhaled corticosteroid use in patients with allergic asthma (49). TA is also associated with fungal spores, such as Alternaria, whose proliferation is increased by floods and storms (47).

The 2019 Global Burden of Disease (GBD) study found that air pollution (outdoor and indoor) is estimated to contribute to about 10% of all noncommunicable disease deaths and is among the top three risk factors for death, with the burden of deaths predominantly in Asia and Africa (50, 51). The Lancet Commission on Pollution and Health linked air pollution to multiple adverse health conditions in children, including low birth weight; noncommunicable diseases such as asthma, cancer, and chronic obstructive pulmonary disease (COPD); and neurodevelopmental disorders (52, 53).

Global warming contributes to air pollution via increases in GHGs and other pollutants released by wildfires and SDSs, with important implications for immune and non-immune diseases (54–61).

Air pollution impacts both the innate and adaptive immune function in various ways (62) ( Figure 2 ). Adaptive T cells such as CD8+ T and CD4+ T cells (Tregs, Th1, and Th2) are altered as are innate immune cells such as innate lymphoid cells type 2 (ILC2), dendritic cells, toll-like receptors (TLRs) and natural killer (NK) cells (63). A study found that ozone-oxidized black carbon caused necroptosis in macrophages, increased levels of reactive oxygen species (ROS), and the expression of inflammatory factors and chemokines (64). Recently, age-related declines in immune function were linked to the accumulation of inhaled atmospheric particulate matter (PM) specifically contained within lung macrophages, which exhibited decreased activation, phagocytic capacity, and altered cytokine production. PM also disrupted the structures of B cell follicles and lymphatic drainage in lung-associated lymph nodes (65). Exposure to wildfire smoke and traffic-related air pollution has been associated with the activation of arylhydrocarbon receptors, toll-like receptors, and nuclear factor (NF)-κB signaling, and the upregulation of pro-inflammatory cytokines such as IL-22 (66). Firefighters have increased IL-6 and IL-12 and decreased IL-10 in their serum 12 hours after exposure to a wildfire (67). The activation of NLRP3 inflammasome and pyroptosis by environmental pollutants has been correlated to numerous diseases (68, 69). For example, perfluoroalkyl substance pollutants have been shown to activate the innate immune system through the absent in melanoma 2 (AIM2) inflammasome (70). In another study, the inflammasome was shown to be activated by micro- and nanoplastics, which are increasingly found in the air (71).

Chronic inflammation, including that triggered by air pollution, also promotes cancer progression. Inflammatory cytokines such as IL-6, TNF-α, and granulocyte macrophage colony-stimulating factor are mediated by air pollution, resulting in low-grade, chronic inflammation (72, 73). Low-grade inflammation fuels tumor progression by enabling immune evasion, angiogenesis, and metastatic dissemination. Air pollutants also mediate oxidative stress, which is characterized by an increase in ROS (74). Exposure to PM with an aerodynamic diameter of ≤2.5 mm (PM_2.5) was found to promote lung cancer by acting on cells that harbor pre-existing oncogenic mutations in healthy lung tissue (75). The discovery of immune checkpoint proteins, such as programmed cell death protein 1 (PD-1)/programmed cell death ligand 1 (PD-L1) and cytotoxic T-lymphocyte associated protein 4 (CTLA-4), represents a significant breakthrough in the field of cancer immunotherapy (76).

Climate change is also increasing global temperatures, with increases in the severity and frequency of heatwaves and the associated morbidity and mortality (113).

During heat stress, high levels of ROS are released ( Figure 2 ). ROS induce oxidative damage and degradation of biomolecules (e.g., proteins, lipids, carbohydrates, and DNA) leading to cellular death, while also increasing the production of heat shock proteins (HSPs), antioxidants, other metabolites, anti-inflammatory cytokines, and stress granules that mitigate the effects of heat stress (114) (115). There is increasing evidence that HSPs can influence the immune system, mediating both pro-inflammatory and anti-inflammatory pathways. For example, HSP70-B29, a bacterial HSP70-derived peptide, has been shown to induce HSP-specific Tregs that suppress arthritis by cross-recognition of their mammalian HSP70 homologs (116). However, HSPs have also been demonstrated to induce the release of pro-inflammatory cytokines such as IL-6 and IL-1 through the NF-kB pathway (117, 118). In primary human keratinocytes and mice, HSP90 inhibition robustly suppressed 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced inflammation by targeting key pro-inflammatory cytokines and signaling pathways, suggesting it may be a potential topical treatment option for immune-mediated skin disease beyond psoriasis (119).

Heat stress has various direct and indirect effects on health and well-being. For example, a study in Australia found a significant increase in childhood asthma emergency department admissions during heatwaves (defined as three consecutive days of extreme heat). Male children and those aged 0–4 years were the most vulnerable (120). In China, exposure to ambient air pollution and high temperatures were independently and jointly associated with asthma risk in early childhood (121). Other direct effects of heat stress include cramps, stroke, increases in cardiovascular disease, and mental health conditions (122). Heat has been shown to cause ventricular-dependent changes that may undermine cardiac health, energy homeostasis, and function (123). Elderly individuals and those with comorbid conditions are at particular risk from heat stress (124).

Heat stress also indirectly affects health outcomes through disruption caused to infrastructures (e.g., power, water, and transport) and via increases in workplace injuries and drownings. Higher temperatures also increase the occurrence of harmful marine algal blooms that release toxins, and food and waterborne diseases (125).

Climate change exacerbates shortages of food and water, which have led to human migration from rural to urban areas or from low- and middle-income countries to affluent countries. The United Nations predicts that close to 70% of the world’s population will live in urban areas by 2050 (126). These migration patterns are associated with increases in asthma and allergy in individuals displaced from a rural environment to a more crowded urban area. Rural areas have higher microbial diversity and exposure to animals, both of which are protective against allergy and asthma. However, migration also exposes individuals to new pollutants and allergens. A study in Brazil found that rural-to-urban migration contributes to the high burden of asthma in urban migrants (127).

The built environment, which encompasses all manufactured or modified structures that provide people with living, working, and recreational spaces, is a critical determinant of allergy and asthma (128) owing to higher levels of indoor pollutants and allergens (129). Climate change is exerting changes in built environments that are expected to drive immune-mediated disease. For example, increased temperatures lead to a lower quality of indoor air. Flooding events result in increased urban indoor dampness, humidity, and mold levels (110). An increase in temperate zones is expected to lead to an increase in rodent populations (130), a matter of concern because mouse allergen is also a critical driver of childhood asthma disparities (131).

Global warming and climate change have substantially endangered food safety for humans and domestic animals. Chemical pollutants contained in foods, such as emulsifiers, coloring agents, and preservatives, can disrupt the epithelial barrier that protects against asthma and allergies (132). Residual detergents found after rinsing foods also damage lung tissue, as shown in human bronchial cell cultures (133). Dioxins and toxic metals such as lead, cadmium, and mercury found in contaminated water are also highly toxic and can lead to decreases in immunity (134, 135).

The human body is an ecosystem or “holobiont”—a concept describing the host (animal or plant) as a community of species linked to other ecosystems and subject to continuous evolutionary pressure (136). Functioning ecosystems provide essential benefits to humanity (137)—sometimes referred to as ecosystem services. Biodiversity (the variety of life including genes, species, and ecosystems) is a key factor in maintaining a healthy and functioning ecosystem and for human health (138). Climate change, habitat destruction, and intensive land use have led to a startling loss of biodiversity, including microbial species (137, 139). Millions of species worldwide could face extinction as a result of climate change in the next few decades (140, 141).

Biodiversity loss associated with climate change can have a huge impact on human health, both directly (through disruption in the food supply or via emerging infectious diseases) and indirectly (by degrading ecosystem health and ecosystem services) (142).

In particular, exposure to a greater diversity of microbes is thought to be a key factor driving the early immune system away from the development of asthma and allergies (143). Maternal exposure to stables during pregnancy, for example, has been found to be associated with increased TNF-alpha and IFN-gamma levels in newborns (144).

Climate change is associated with increased mental health burden and stress (145). In individuals with persistent emotional stress and greater negative moods, allergy flares are more frequent (146). The stress hormones, including glucocorticoids, epinephrine, and norepinephrine, are thought to be involved in psychological stress-induced asthma exacerbation (147). A study of 763 Japanese mother-child pairs used 12 specific behavioral patterns as stress indicators and found that maternal chronic irritation and anger were associated with the risk of childhood asthma (148). In adolescents, stressors such as poverty, neighborhood stress, and school stress were individual predictors of emergency department visits for asthma (149). In 2021, a survey of children and young adults in 10 countries found that there was widespread climate anxiety and dissatisfaction with government responses to climate change (150).

We have outlined the complex effects that climate change is having on environmental exposures that in turn cause immune dysregulation and its associated diseases, including asthma, allergies, autoimmune diseases, and cancers ( Figure 1 ). Research into the pathophysiology of immune-mediated diseases has provided a greater understanding of their mechanisms and has led to the development of novel drugs (151). However, in addition to this individualized treatment approach, multisectoral, multidisciplinary, and multilevel efforts are urgently needed to mitigate and adapt to the effects of climate change-related exposures ( Figure 6 ).

Mitigation refers to primary preventions intended to cut or prevent the emission of greenhouse gases (e.g., using an electric car or electrifying a housing unit) thus limiting the magnitude of future warming. Adaptation is a form of secondary prevention intended to reduce vulnerability to climate change impacts, such as going to cooling centers during heat stress (e.g., see www.marinhhs.org/cooling-centers) or using a filter in a home to decrease asthma and allergies (152).

Climate change presents an existential threat to the health of humans, animals, and the entire ecosystem. The changing exposome has led to an increased risk of major diseases associated with immune dysregulation, including asthma, allergies, cancers, and autoimmune diseases. While progress has been made in the development of therapeutic options to treat these disorders, these approaches are inadequate to meet the challenges posed by climate change.

We must fully recognize that planetary health is the basis of human health. Individuals, organizations, and nations need to work toward systematically mitigating the health effects of climate change, adapting to these changes, and promoting planetary health to improve immune health and decrease the immense burden of immune-mediated disease. Fundamentally, there is an urgent need to develop and implement sustainable practices and reduce the use of fossil fuels to benefit planetary health for succeeding generations. We suggest more collaborative research on the impact of climate change and policies for climate change mitigation on asthma and allergy outcomes.

Socioeconomically disadvantaged groups, such as immigrants with limited language proficiency, communities of color, indigenous groups, and outdoor workers on daily wages, face the brunt of the impact of climate change because of poor housing infrastructure, proximity to highly polluted areas, or poor access to medical care. Children, pregnant women, the elderly, individuals with preexisting conditions, and people with disabilities are also at greater risk from the adverse health effects of climate change. Justice, equity, diversity, and inclusion (JEDI) considerations should be integral within climate adaptation planning to address existing disparities exacerbated by climate change.