Alpha7 nicotinic acetylcholine receptor participates in the effect of dexmedetomidine on Treg cell differentiation

The anti-inflammatory effect of dexmedetomidine can be mediated through alpha7 nicotinic acetylcholine receptor (α7nAChR). However, it remains unknown whether α7nAChR is involved in mediating the effects of dexmedetomidine on CD4⁺T cell differentiation. The study aims to explore whether dexmedetomidine can affect CD4⁺T cell differentiation through α7nAChR.

Naïve CD4⁺T cells obtained from mouse spleens were incubated with different concentrations of dexmedetomidine for 3 days in vitro. The percentages of helper T (Th)1, Th2, Th17, and regulatory T (Treg) cells were determined by flow cytometry. The corresponding transcription factors T-bet (Th1), GATA-3 (Th2), ROR γt (Th17), and Foxp3 (Treg) were detected using quantitative real-time PCR. Mice with tibia fracture were pretreated with dexmedetomidine or methyllycaconitine (MLA, an α7nAChR antagonist) for 48 h in vivo. The percentages of Th1, Th2, Th17, and Treg cells were determined. Naïve CD4⁺T cells were incubated with dexmedetomidine and MLA in vitro and Treg cells were detected. The level of interleukin (IL)-10 secreted by Treg cells was quantified by an enzyme-linked immunosorbent assay.

Dexmedetomidine administration, both in vitro and in vivo, suppressed Th1 cell differentiation along with its transcription factor T-bet, while promoting Treg cell differentiation and upregulating Foxp3. Conversely, MLA reversed these effects of dexmedetomidine on Th1 and Treg cell differentiation in vivo. In vitro, MLA also attenuated the dexmedetomidine-induced enhancement of Treg cell differentiation and the associated IL-10 secretion.

Dexmedetomidine promotes Treg cell differentiation while inhibiting Th1 cell differentiation. This regulatory activity on Treg cells may be mediated through the α7nAChR pathway.