Chronic asthma is characterised by the accumulation of neutrophils in the lungs, which are key drivers in chronic lung inflammation [1,2]. Moreover, neutrophil accumulation density correlates with disease severity . The high levels of neutrophils are a result of granulocyte-macrophage colony-stimulating factor (GM-CSF)-signalling, which promotes the development of alveolar macrophages (AM) and lung dendritic cell (DC)-dependent induction of Th2/Th17 cell immunity . GM-CSF-deficient animals endure profound impact on the lungs caused by the absence of AM . However, reconstruction of AM in these deficiency models prevented this damage . Acute lung inflammation driven by Th2/ILC2 responses has been investigated before , whereas the long-term chronic asthma pathology was thus far unknown. To this end, the current study investigated the role of granulocyte-macrophage colony-stimulating factor (GM-CSF) in the development of neutrophil-mediated chronic asthma .
The GM-CSF-driven lung DC–T-cell circuit in chronic asthma was studied in different experimental animal models of chronic asthma. Nobs et al. combined these models with AM-reconstruction of global GM-CSF receptor- and cell type-specific knockout mice .
Results indicated a crucial regulating role of GM-CSF signalling in the accumulation of neutrophils in the lungs. Furthermore, GM-CSF signalling regulated DC activation, antigen uptake, and transport to the lung-draining lymph node. Additionally, lung DC–T-cell interaction, Th2 and Th17 polarisation, and induction of T-cell immunity was driven by GM-CSF signalling, which altogether led to chronic lung inflammation in asthma models.
In conclusion, the current study suggests a GM-CSF-dependent inflammatory circuit triggering lung DC–T-cell interaction leading to chronic lung disease. This circuit promoted T cell-dependent recruitment of neutrophils to the lungs, leading to chronic lung inflammation [1,2]. Thus, GM-CSF was identified as a potential therapeutic target in chronic asthma research and possibly in other chronic inflammatory lung diseases.
DOI: 10.1016/j.jaci.2020.12.638 Samuel Philip Nobs PhD, Lea Pohlmeier MSc, Fengqi Li PhD, Merve Kayhan MSc, Burkhard Becher PhD, Manfred Kopf PhD.
- Nobs SP, Pohlmeier L, Li F, et al. GM-CSF instigates a dendritic cell – T cell inflammatory circuit that drives chronic asthma development, Journal of Allergy and Clinical Immunology; 2021, doi: 10.1016/j.jaci.2020.12.638.
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