Cannabinoid receptor 2 signal promotes type 2 immunity in the lung
Tingting Liu,
Jiaqi Liu,
Hongjie Chen,
Xin Zhou,
Wei Fu,
Ying Cao,
Jing Yang
Affiliations
Tingting Liu
Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, 100871, China
Jiaqi Liu
State Key Laboratory of Membrane Biology, School of Life Sciences, Peking University, Beijing, 100871, China
Hongjie Chen
Peking University-Tsinghua University-National Institute of Biological Sciences Joint Graduate Program, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, 100871, China
Xin Zhou
Department of General Surgery, Peking University Third Hospital, Beijing, 100191, China; Peking University Third Hospital Cancer Center, Beijing, 100191, China
Wei Fu
Department of General Surgery, Peking University Third Hospital, Beijing, 100191, China; Peking University Third Hospital Cancer Center, Beijing, 100191, China
Ying Cao
Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, 100871, China
Jing Yang
Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, 100871, China; State Key Laboratory of Membrane Biology, School of Life Sciences, Peking University, Beijing, 100871, China; Peking University-Tsinghua University-National Institute of Biological Sciences Joint Graduate Program, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, 100871, China; IDG/McGovern Institute for Brain Research, Peking University, Beijing, 100871, China; Peking University Third Hospital Cancer Center, Beijing, 100191, China; Institute of Molecular Physiology, Shenzhen Bay Laboratory, Shenzhen, 518055, China; Corresponding author. Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, 100871, China.
Type 2 immunity in the lung protects against pathogenic infection and facilitates tissue repair, but its dysregulation may lead to severe human diseases. Notably, cannabis usage for medical or recreational purposes has increased globally. However, the potential impact of the cannabinoid signal on lung immunity is incompletely understood. Here, we report that cannabinoid receptor 2 (CB2) is highly expressed in group 2 innate lymphoid cells (ILC2s) of mouse and human lung tissues. Of importance, the CB2 signal enhances the IL-33-elicited immune response of ILC2s. In addition, the chemogenetic manipulation of inhibitory G proteins (Gi) downstream of CB2 produces a similarly promotive effect. Conversely, the genetic deletion of CB2 mitigates the IL-33-elicited type 2 immunity in the lung. Also, such ablation of the CB2 signal ameliorates papain-induced tissue inflammation. Together, these results have elucidated a critical aspect of the CB2 signal in lung immunity, implicating its potential involvement in pulmonary diseases.
