Chronic nicotine stimulation modulates the immune response of mucosal T cells to Th1-dominant pattern via nAChR by upregulation of Th1-specific transcriptional factor.

Inflammatory bowel disease (IBD) consists of Crohn's disease (CD) and ulcerative colitis (UC). The etiology has not been clarified yet, but immune disorder is thought to be involved in the pathogenic physiology. Recently, general consensus has been reached that CD and UC are distinct, especially in respect of the immune response. Interestingly, smoking has diverse effects on CD, Th1-type enteritis, and on UC, Th2-type. However, the mechanisms remain obscure. Therefore, we hypothesized that nicotine altered the distinct immune responses in each form of IBD to affect their pathophysiology. In this study, we first demonstrated by RT-PCR analysis that human lamina propria T (LPT) cells had nicotinic acetylcholine receptor (nAChR), and express alpha7 nAChR subunit universally. In addition, the expression of T-bet mRNA in human LPT cells was significantly upregulated after the culture with 10(-7)M and 10(-5)M nicotine for 9 days, while chronic nicotine stimulation showed negligible effect on the expression of GATA-3 mRNA by real-time PCR. The effect of nicotine was inhibited by mecamylamine (MEC). These results suggested that nicotine could modulate the immune balance to Th1-dominant via nAChR in the intestine, to improve Th2-type enteritis. This may provide the experimental evidence for the fact that nicotine has a beneficial influence on UC, and exacerbates CD. Furthermore, it is of great interest that nicotine acts oppositely on CD and UC by modulation of the mucosal immune balance via the neurotransmitter receptor.