1-Minute Summary: GM-CSF instigates a dendritic cell – T cell inflammatory circuit that drives chronic asthma development.

Expert Name
Dr S.P. Nobs, Dr L. Pohlmeier, Dr F. Li, et al.

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 [3]. 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 [4]. GM-CSF-deficient animals endure profound impact on the lungs caused by the absence of AM [5]. However, reconstruction of AM in these deficiency models prevented this damage [6]. Acute lung inflammation driven by Th2/ILC2 responses has been investigated before [7], 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 [1].

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 [1].

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.

References

  1. 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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