(A) Lymphocyte subpopulations in ALNs were measured using flow cytometry. theirex vivocytokine 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 ON 146040 we suggest that the innate ILC2 cells are important additional players in the development of TDI-induced asthma. Keywords:Toluene diisocyanate, mice, dendritic cells, innate lymphoid cells, immune system, asthma, bronchoalveolar lavage fluid, methacholine, T-lymphocyte == INTRODUCTION == Mostly, asthma develops during childhood, depending on sensitization to common environmental allergens. Yet, asthma can also emerge later Rabbit Polyclonal to KCNK1 in life. This late-onset asthma in adults is often non-allergic and tends to be more severe compared to early-onset asthma.1Of adults with late-onset asthma, 5%25% suffer from occupational asthma, which is a consequence of exposure to harmful chemical agents at the workplace, such as diisocyanates.2 Skin exposure to diisocyanates, such as toluene diisocyanate (TDI), induces systemic T cell-dependent sensitization.3,4After sensitization, exposure to low concentrations of diisocyanates can result in an asthmatic airway response.5,6Tarkowskiet al.7and Devoset al.8have shown in severe combined immune-deficient mice, which lack T and B cells, that ventilatory and inflammatory airway responses in chemical-induced asthma are lymphocyte dependent. Interestingly, these responses were not only type 2 helper T (Th2) cell dependent but also showed the characteristics of a Th1 response, such as elevated interferon (IFN)- levels.9However, lymphocytes were not present in the bronchoalveolar lavage (BAL) fluid of mice with asthma-like symptoms.7On the other ON 146040 hand, some studies were able to observe lymphocytes in BAL fluid. These contradictory results question the exact role and importance of lymphocytes in chemical-induced asthma.10,11,12Until now, the known underlying mechanisms cannot completely explain ON 146040 respiratory responses in diisocyanate-induced asthma. Animal models of allergic asthma have also observed that T and B cells alone cannot explain observed asthmatic responses. For example, studies in RAG-deficient mice (no T and B cells) showed persistent eosinophilic airway inflammation and Th2 cytokine production, after administration of house dust mite (HDM). This suggests the involvement of non-T or B cells, such as innate lymphoid cells (ILCs). In these models, ILC2 are proposed as the additional key player. ILC2 are the most common subgroup of ILC in HDM-challenged mice and have a Th2-like cytokine expression pattern (interleukin [IL]-5, IL-4 and IL-13) in response to IL-33, IL-25 and thymic stromal lymphopoietin (TSLP). They are proposed to be involved in the very early phase after allergen exposure.13,14,15,16Additionally, ILC1 and ILC3 are 2 other ILC subsets that have been described, respectively characterised by a Th1-and a Th17-like cytokine pattern. These subsets are associated with non-allergic late-onset asthma, caused by exposure to pollutants, infections, occupational agents and intensive exercise.13,15,16,17Yet, the role of the ILC subsets in chemical-induced asthma, specifically in diisocyanate-induced asthma, is not well studied. In addition to ILCs, dendritic cells (DCs) are recognised as crucial cells during both the sensitization and effector phases of allergic asthma. DCs are important antigen presenting cells in the lungs, bridging innate and adaptive immunity.18Different DC subsets are identified in the lung based on the presence of surface markers, such as CD11c, CD103, CD11b, CD64 and Siglec-H. Using these markers, DCs are divided into conventional DC ON 146040 (CD103+CD11bconventional dendritic cell.
