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
Centre for Environment and Health, Department of Public Health and Primary Care, University of Leuven, Leuven, Belgium.
Laboratory of Respiratory Diseases and Thoracic Surgery, Department of Chronic Diseases and Metabolism, University of Leuven, Leuven, Belgium.
Allergy Asthma Immunol Res. 2021 Mar;13(2):295-311. 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.
暴露于低浓度甲苯二异氰酸酯（TDI）会引发免疫介导的化学性诱导哮喘。适应性免疫系统的作用已得到充分研究；然而，固有免疫细胞在化学性诱导哮喘病理生理学中的作用仍未明确。本研究的目的是在化学性诱导哮喘的小鼠模型中研究固有淋巴细胞（ILC）和树突状细胞（DC）的作用。
在第1天和第8天，用0.5% TDI或赋形剂丙酮橄榄油（AOO；2:3）对BALB/c小鼠进行皮肤处理（每只耳朵20μL）。在第15、17、19、22和24天，用0.01% TDI或AOO（1:4）对小鼠进行口咽激发。在最后一次激发后一天，评估对乙酰甲胆碱的气道高反应性（AHR），随后评估肺部炎症和免疫相关参数，包括支气管肺泡灌洗液中的细胞因子模式、淋巴结中的淋巴细胞亚群及其细胞因子产生谱、血液免疫球蛋白以及肺中的DC和ILC亚群。
多次气道暴露于TDI后，无论先前是否进行皮肤致敏，DC和ILC2均被募集到肺部。然而，仅用TDI进行先前的皮肤致敏会导致AHR和主要的嗜酸性气道炎症，并伴有典型的2型辅助性T（Th2）细胞因子谱。
TDI诱导的哮喘由主要的2型免疫反应介导，涉及适应性Th2细胞。然而，从我们的研究中我们认为固有ILC2细胞是TDI诱导哮喘发展中的重要额外参与者。
