Cytokine-induced alterations of BAMBI mediate the reciprocal regulation of human Th17/Treg cells in response to cigarette smoke extract.

In CD4+ T helper (Th) cells, transforming growth factor β (TGF‑β) is indispensable for the induction of both regulatory T (Treg) and interleukin‑17‑producing effector T helper (Th17) cells. Although BMP and activin membrane‑bound inhibitor (BAMBI) is part of a rheostat‑like mechanism for the regulation of TGF‑β signalling and autoimmune arthritis in mouse models, the underlying activity of BAMBI on the human Th17/Treg cell axis, particularly during exposure to cigarette smoke, remains to be elucidated. The present study aimed to further characterize BAMBI expression in human CD4+ cells, as well as immune imbalance during activation and cigarette smoke exposure. Results from the present study indicated that exposure to cigarette smoke extract partially suppressed Treg differentiation and promoted Th17 cell generation under stimulation by anti‑CD3/28 antibodies and TGF‑β1. Additionally, exposure to cigarette smoke induced an inhibition of phosphorylated‑Smad2/Smad3, which may have arisen from a concomitant enhancement of BAMBI expression. In conclusion, human BAMBI may function as a molecular switch to control TGF‑β signalling strength and the Th17/Treg cell balance, which may be used not only as a biomarker but also as a target of new treatment strategies for maintaining immune tolerance and for the treatment of smoking‑induced immune disorders.