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

• Published in: Allergy, asthma & immunology research Vol. 13; no. 2; pp. 295 - 311
• Main Authors: Pollaris, Lore, Decaesteker, Tatjana, Van den Broucke, Sofie, Jonckheere, Anne Charlotte, Cremer, Jonathan, Verbeken, Erik, Maes, Tania, Devos, Fien C, Vande Velde, Greetje, Nemery, Benoit, Hoet, Peter H M, Vanoirbeek, Jeroen A J
• Format: Journal Article
• Language: English
• Published: Korea (South) Korean Academy of Asthma, Allergy and Clinical Immunology 01.03.2021; The Korean Academy of Asthma, Allergy and Clinical Immunology; The Korean Academy of Pediatric Allergy and Respiratory Disease
• Subjects: Acetone; Adaptive systems; Alveoli; Asthma; Bronchus; Cytokines; Dendritic cells; Exposure; Helper cells; Hypersensitivity; Immune response; Immune system; Immunoglobulins; Leukocytes (eosinophilic); Low concentrations; Lungs; Lymph nodes; Lymphocytes; Lymphocytes T; Lymphoid cells; Methacholine; Olive oil; Original; Respiratory tract; Respiratory tract diseases; Subpopulations; Toluene; Toluene diisocyanate; Toluene diisocyanates; dendritic cells; bronchoalveolar lavage fluid; immune system; T-lymphocyte; Toluene diisocyanate; asthma; innate lymphoid cells; methacholine; mice
• ISSN: 2092-7355; 2092-7363
• DOI: 10.4168/AAIR.2021.13.2.295

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. 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 cytokine production profile, blood immunoglobulins and DC and ILC subpopulations in the lungs. 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. 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.