. 2018 Jun 26;18(3):e22. doi: 10.4110/in.2018.18.e22

Table 5. Potential effects of SHS/direct CS/direct or secondary nicotine on Treg function.

Tregs	Effects of SHS/direct CS/direct or secondary nicotine
Tregs	In man, CS exposure enhanced the function of Tregs in the lungs (162,163,164)^(H,H,M). A possible mechanism by which CS enhances Treg function is the ability of CS to induce PD-L1/2 on antigen-presenting cells, resulting in increased engagement to PD-1 on Tregs, enhancing the immunosuppressive function of Tregs (56,58,165)^(M/H,H,H).
In mice, Tregs express the α7 nicotinic acetylcholine receptor and upon binding to nicotine, there is an upregulation of both the transcription factor Foxp3 and the cell surface molecule CTLA-4, proteins that characterize Tregs and dampen Foxp3-negative T effector cell activity, respectively (164)^(M). By producing TGFβ and IL-10, CS-induced Tregs can further suppress M1 macrophage activation against MTB as well as induce macrophages to differentiate to the M2/deactivated phenotype (51)^(M/H). Nicotine induced murine Tregs to produce TGFβ and nicotine-exposed Tregs impair macrophage activity against MTB in murine macrophages (68)^(M/H).

Tregs

Effects of SHS/direct CS/direct or secondary nicotine

Tregs

In man, CS exposure enhanced the function of Tregs in the lungs (162,163,164)^(H,H,M). A possible mechanism by which CS enhances Treg function is the ability of CS to induce PD-L1/2 on antigen-presenting cells, resulting in increased engagement to PD-1 on Tregs, enhancing the immunosuppressive function of Tregs (56,58,165)^(M/H,H,H).

In mice, Tregs express the α7 nicotinic acetylcholine receptor and upon binding to nicotine, there is an upregulation of both the transcription factor Foxp3 and the cell surface molecule CTLA-4, proteins that characterize Tregs and dampen Foxp3-negative T effector cell activity, respectively (164)^(M). By producing TGFβ and IL-10, CS-induced Tregs can further suppress M1 macrophage activation against MTB as well as induce macrophages to differentiate to the M2/deactivated phenotype (51)^(M/H). Nicotine induced murine Tregs to produce TGFβ and nicotine-exposed Tregs impair macrophage activity against MTB in murine macrophages (68)^(M/H).

M, murine; H, human; M/H, murine and human.