Involvement of Innate Lymphoid Cells and Dendritic Cells in a Mouse Model of Chemical-induced Asthma

Abstract

Purpose Exposure to low concentrations of toluene diisocyanate (TDI) leads to immune-mediated chemical-induced asthma. The role of the adaptive immune system has already been thoroughly investigated; nevertheless, the involvement of innate immune cells in the pathophysiology of chemical-induced asthma is still unresolved. The aim of the study is to investigate the role of innate lymphoid cells (ILCs) and dendritic cells (DCs) in a mouse model for chemical-induced asthma. Methods On days 1 and 8, BALB/c mice were dermally treated (20 µL/ear) with 0.5% TDI or the vehicle acetone olive oil (AOO; 2:3). On days 15, 17, 19, 22 and 24, the mice received an oropharyngeal challenge with 0.01% TDI or AOO (1:4). One day after the last challenge, airway hyperreactivity (AHR) to methacholine was assessed, followed by an evaluation of pulmonary inflammation and immune-related parameters, including the cytokine pattern in bronchoalveolar lavage fluid, lymphocyte subpopulations of the lymph nodes and their ex vivo cytokine production profile, blood immunoglobulins and DC and ILC subpopulations in the lungs. Results Both DC and ILC2 were recruited to the lungs after multiple airway exposures to TDI, regardless of the prior dermal sensitization. However, prior dermal sensitization with TDI alone results in AHR and predominant eosinophilic airway inflammation, accompanied by a typical type 2 helper T (Th2) cytokine profile. Conclusions TDI-induced asthma is mediated by a predominant type 2 immune response, with the involvement of adaptive Th2 cells. However, from our study we suggest that the innate ILC2 cells are important additional players in the development of TDI-induced asthma.

Assessment of personal inhalation and skin exposures to polymeric methylene diphenyl diisocyanate during polyurethane fabric coating

“…Repeated MDI skin exposure is required to induce sensitization, as demonstrated in several animal models of isocyanate asthma (Hoffmann et al, 2010; Pollaris et al, 2021; Wisnewski et al, 2011). In addition to the concentration and total dose, the frequency and timing of exposure (interval between exposure) are also important determinants of sensitization, with greater number of exposures and longer intervals typically promoting stronger immune responses.…”

Lung Gene Expression Suggests Roles for Interferon-Stimulated Genes and Adenosine Deaminase Acting against RNA-1 in Pathologic Responses to Diisocyanate

“…Diisocyanate activation of the innate arm of the immune system has been described by several investigators and may be a differential pathway by which certain LMW allergens, especially reactive chemicals, cause asthma . Pro-inflammatory myeloid and innate lymphoid cell (γδ T-cells, ILC2) responses have been described in vitro with human cells and in vivo in limited murine studies. ,,− While diisocyanates can stimulate innate immune responses, mechanisms connecting these responses to the clinical syndrome experienced by affected workers, with long-lived memory and increasing hypersensitivity upon repeated exposures (hallmarks of Type I Hypersensitivity) remain challenging to define.…”