Chemical-Induced Asthma Mechanisms in Murine Models

Chemical-induced asthma in murine models has shed light on how low-molecular-weight agents such as diisocyanates trigger immune sensitisation and airway dysfunction. Dermal or inhalation exposure to reactive haptens leads to covalent conjugation with endogenous proteins—most notably albumin—forming neoantigens that are processed by antigen-presenting cells. The ensuing Th2-polarised response drives eosinophilic inflammation, airway hyperresponsiveness and remodelling. Key mediators include epithelial alarmins (for example IL-33), type 2 innate lymphoid cells (ILC2s) and dendritic cell subsets that orchestrate the transition from innate to adaptive immunity. Recent single-cell and genetic studies have delineated macrophage heterogeneity, microRNA regulation of antigen presentation and epithelial–immune crosstalk. Insights from absorption, distribution, metabolism and excretion (ADME) research underscore the importance of local protein adduct formation in determining portal-of-entry toxicity. Collectively, murine data underpin global efforts to develop targeted therapies and refine occupational safety standards for respiratory sensitising chemicals.

Research from Nature Portfolio

Recent studies have applied state-of-the-art technologies to dissect chemical asthma mechanisms at unprecedented resolution. A landmark single-cell profiling investigation of diisocyanate-challenged mice identified a subset of monocyte-derived alveolar macrophages with profibrotic and proinflammatory gene signatures that perpetuate neutrophil recruitment and parenchymal remodelling upon repeated exposures. Another work employed epithelial-specific knockout of interleukin-33 to demonstrate that loss of this alarmin markedly reduces eosinophilic airway inflammation and hyperresponsiveness, firmly placing epithelial IL-33 at the apex of Th2 initiation in chemical asthma. A third report revealed that upregulation of microRNA-21 in lung-resident dendritic cells enhances presentation of isocyanate–protein adducts and promotes Th2 differentiation; pharmacological inhibition of microRNA-21 prior to challenge attenuated IL-4 and IL-13 production, alleviating airway constriction. Together, these findings define novel cellular and molecular targets for intervention in chemical-induced asthma.

Chemical-Induced Asthma Mechanisms in Murine Models publication trend

The graph below shows the total number of articles in chemical-induced asthma mechanisms in murine models across all publications each year (not limited to Nature Index journals).

Technical terms

Hapten: A small reactive molecule that covalently binds to proteins, creating a neoantigen.

Dendritic cell: A professional antigen-presenting cell that processes haptens and activates T lymphocytes.

Innate lymphoid cell type 2 (ILC2): A lymphocyte-like innate immune cell that secretes type 2 cytokines (IL-5, IL-13) without antigen specificity.

Bronchoalveolar lavage (BAL): A technique for sampling cells and soluble mediators from the lower respiratory tract.

Airway hyperresponsiveness (AHR): An exaggerated bronchoconstrictive response to non-specific stimuli, indicative of asthma-like airway dysfunction.

References

1. Absorption, distribution, metabolism, and excretion of methylene diphenyl diisocyanate and toluene diisocyanate: Many similarities and few differences. Toxicology and Industrial Health (2022).
2. Immune sensitization to methylene diphenyl diisocyanate (MDI) resulting from skin exposure: albumin as a carrier protein connecting skin exposure to subsequent respiratory responses. Journal of Occupational Medicine and Toxicology (2011).
3. Involvement of Innate Lymphoid Cells and Dendritic Cells in a Mouse Model of Chemical-induced Asthma. Allergy Asthma and Immunology Research (2021).