Additionally, although MR agonist had pro-proliferative effect on CD8+ Tregs resembling that of CSE, MRs did not seem to affect CD8+ Treg apoptosis, indicating that CSE promotes the apoptosis of CD8+ Treg cells in a MR-independent signaling pathway: Firstly, since we have previously reported that the expression of anti-inflammatory α7 nAChR by circulating CD4+ T cells was reduced in smokers with COPD [12], CSE may disrupt a signaling pathway of nicotinic but not muscarinic acetylcholine receptor, contributing to the apoptosis of CD8+ Tregs in susceptible populations. The gene discussed is CD4; the disease is chronic obstructive pulmonary disease.