Nicotine Mediated Regulatory Effect On Collagen Induced Arthritis And The Influence Of Nicotine To The Induction And Function Of In Vitro Cultured Th17

In recent decade, the discovery that proinflammatory responses are controlled by neural circuits linked together the immunology and the neurobiology. That means the immune systems are no longer thought as an entire anonymous one. And this reflex control system is so called acetylcholine anti-inflammatory pathway.Acetylcholine receptors, as the member of the pathway, play a great role in the anti-inflammatory reflex. a7nAChR, a member of the acetylcholine receptors family, is widely expressed in the neural system. It can form homopentameric and heteropentameric receptors in neurons, and function as ligand-gated ion channels that mediate fast signal transmission at synapses. Apart from the neural system, a 7 nAChR is also found expressed on the immune cells, including monocytes, macrophages, T, B lymphocytes and dendritic cells. Activation by non-selective (nicotine) or selective agonist (GTS-21 or choline) could induce a serial number of signal cascades, downregulate the activity of nucleus transcriptor NF-κB and the expression of TLR4; therefore, attenuate the transcription of proinflammatory factors.The present study used the collagen induced arthritis model to evaluate the regulatory effect on CIA immune system. Compared with the control group, mice supplied with oral nicotine showed a more attenuated signs of arthritis and delayed severity progress on arthritis. Spleen Th17 ratio of mice supplemented with nicotine was less than that of control group (12.53% vs 7.63%), and cytokines mRNA levels in experimental group of IL-17A as well as IL-21 and IL-6 were much lower than that of control group. Moreover, nicotine treatment group also displayed a more reduced plasma TNFa level compared to the control group.Meantime, to understand the regulatory effect mechanism of acetylcholine receptors on CIA mice, we further explored the a7 nAChR expression on ex vivo Thl7 cells. In all of the cells assayed, the ratio of nAChR positive Thl7 cells was 8.49%; about 25.64% of IL-17A-cells were nAChR positive. Thereafter, we purified the Thl7 cells using antibody tetramers, the ratio of IL-17A+ cells after selection was 58.49%. Moreover, cells treated with 10-6M nicotine expressed less IL-17A. And less amount of IL-17A were found in the supernatant of cells treated with nicotine (546.99±17.73 pg/ml vs.669.36±21.15 pg/ml). This study steered together the acetylcholine receptors and collagen induced arthritis, providing an experimental basis for the treatments aimed acetylcholine receptors, while further linking the acetylcholine receptors with Th17 cells. Therefore, provide a new theoretical basis for the acetylcholine anti-inflammatory pathway.