In addition, CAP activation reduces neutrophil CD11b expression, and diminishes neutrophil trafficking to sites of inflammation in skin, joint and gut. Further, subdiaphragmatic vagotomy increases and pharmacologic CAP agonists decrease in vitro T cell proliferation and secretion of IFNc, TNF, and IL-6. In vitro culture of na? ��ve T cells with nicotine enhances the effect of cell activation-induced INT-747 expression of FoxP3, and nicotine treatment markedly increases the influx of CD4 + CD25 + FoxP3 + T regulatory cells into the gut in rodent oxalazone-induced colitis. In rodent hapten-induced colitis, disease severity is worsened by subdiaphragmatic vagotomy, correlated with reductions in FoxP3 + Tregs. Over time the proinflammatory effect of vagotomy wanes, accompanied by recovery of Treg numbers. Finally, effects on B cells have also recently been demonstrated. In response to VNS or cholinergic agonists, splenic marginal zone B cells exhibit reduced trafficking to the splenic red pulp and peri-follicular areas during their maturation process. This migratory arrest is driven by changes in CD11b, and is associated with reduced secretion of antibodies. These inhibitory effects on mononuclear cell mediator release, neutrophil trafficking, and T and B cell function may be contributing to the improvements in CIA disease measures we have observed. Our use of electrical neurostimulation to elicit CAP activation in CIA is supported by several prior studies. Because of the critical role of the a7nAChR and its expression within the fibroblast-like synoviocytes of inflamed human synovium we previously studied the course of CIA in mice with targeted disruption of the receptor gene. When compared to wild type littermates, knockout animals had a faster onset, greater incidence, and worsened severity of disease; increased radiographic evidence of bone destruction, increased histological joint inflammation, elevated in vitro release of Th1 cytokines from cultured splenocytes and increased systemic Ginsenoside-F2 levels of Monocyte Chemotactic Peptide -1 and TNF. Conversely, the course and severity of murine CIA was ameliorated by systemic treatment with the selective a7nAChR agonist AR-R17779.