GTS-21, an α7-nicotinic acetylcholine receptor agonist, modulates Th1 differentiation in CD4+ T cells from patients with rheumatoid arthritis

GTS-21 (also known as DMBX-anabaseine), a selective α7 nicotinic acetylcholine receptor (α7nAChR) agonist, has previously been found to inhibit the inflammation associated with rheumatoid arthritis (RA). RA is an autoimmune disease, where an abnormal immune system plays a critical role in the occurrence and development of synovium inflammation and bone damage. However, prior to this study, the immunological mechanism by which GTS-21 protects against RA had not been elucidated. In the present study, the effects of GTS-21 on T helper 1 (Th1) cells, which have an important role in the inflammation associated with RA, were investigated. Peripheral blood mononuclear cells (PBMCs) and cluster of differentiation (CD)4+ T cells were separated from patients with RA, and the effects of GTS-21 on PBMCs stimulated with anti-CD3/-CD28 antibodies and CD4+ T cells were investigated in the context of Th1-cell differentiation. ELISA was used to analyze interferon (IFN)-γ expression and flow cytometric analysis was used to detect the percentage of IFN-γ+ CD3+CD8- T cells. In addition, western blotting was employed to detect the levels of the T-box transcription factor TBX21, which is a Th1 cell-specific transcription factor. The present study showed that GTS-21 reduced IFN-γ production in PBMCs from patients with RA. Under conditions of Th1-cell differentiation, GTS-21 reduced the percentage of IFNγ+CD3+CD8- T cells and IFN-γ production in the culture supernatant and also inhibited the expression of the Th1 cell-specific transcription factor TBX21. The effects of GTS-21 were blocked by the α7nAchR antagonist α-bungarotoxin, which increased the expression of IFN-γ and TBX21. This study demonstrated that GTS-21 is able to inhibit RA Th1-cell differentiation through activation of the α7nAchR.