CD200-CD200R immune checkpoint engagement regulates ILC2 effector function and ameliorates lung inflammation in asthma

Pedram Shafiei-Jahani, Doumet Helou, Benjamin Hurrell, Emily Howard, Christine Quach, Jacob Painter, Lauriane Galle-Treger, Meng Li, Yong-Hwee Loh, Omid Akbari (2021) CD200-CD200R immune checkpoint engagement regulates ILC2 effector function and ameliorates lung inflammation in asthma Nat Commun (IF: 15.7) 12(1) 2526

Abstract

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.

Links

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8100131
http://www.ncbi.nlm.nih.gov/pubmed/33953190
http://dx.doi.org/10.1038/s41467-021-22832-7

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