CD200-CD200R immune checkpoint engagement regulates ILC2 effector function and ameliorates lung inflammation in asthma.
Pedram Shafiei-JahaniDoumet Georges HelouBenjamin P HurrellEmily HowardChristine QuachJacob D PainterLauriane Galle-TregerMeng LiYong-Hwee Eddie LohOmid AkbariPublished in: Nature communications (2021)
The prevalence of asthma and airway hyperreactivity (AHR) is increasing at an alarming rate. Group 2 innate lymphoid cells (ILC2s) are copious producers of type 2 cytokines, which leads to AHR and lung inflammation. Here, we show that mouse ILC2s express CD200 receptor (CD200R) and this expression is inducible. CD200R engagement inhibits activation, proliferation and type 2 cytokine production, indicating an immunoregulatory function for the CD200-CD200R axis on ILC2s. Furthermore, CD200R engagement inhibits both canonical and non-canonical NF-κB signaling pathways in activated ILC2s. Additionally, we demonstrate both preventative and therapeutic approaches utilizing CD200R engagement on ILC2s, which lead to improved airway resistance, dynamic compliance and eosinophilia. These results show CD200R is expressed on human ILC2s, and its engagement ameliorates AHR in humanized mouse models, emphasizing the translational applications for treatment of ILC2-related diseases such as allergic asthma.
Keyphrases
- cell proliferation
- nk cells
- pi k akt
- social media
- signaling pathway
- chronic obstructive pulmonary disease
- oxidative stress
- lung function
- mouse model
- endothelial cells
- induced apoptosis
- allergic rhinitis
- cystic fibrosis
- dendritic cells
- risk factors
- epithelial mesenchymal transition
- binding protein
- endoplasmic reticulum stress
- air pollution
- monoclonal antibody
- replacement therapy
- pluripotent stem cells