Ulcerative colitis (UC) is a chronic inflammatory bowel disease. Several studies have demonstrated that α7 nicotinic acetylcholine receptors (α7nAChRs) exert anti-inflammatory effects on immune cells and nicotine suppress UC onset and relapse. Plasmacytoid dendritic cells (pDCs) reportedly accumulate in the colon of UC patients. Therefore, we investigated the pathophysiological roles of α7nAChRs on pDCs in the pathology of UC using oxazolone (OXZ)-induced Th2-type colitis with BALB/c mice. 2-deoxy-D-glucose, a central vagal stimulant suppressed OXZ colitis, and nicotine also ameliorated OXZ colitis with suppressing Th2 cytokines, which was reversed by α7nAChR antagonist methyllycaconitine. Additionally, α7nAChRs were expressed on pDCs, which were located very close to cholinergic nerve fibers in the colon of OXZ mice. Furthermore, nicotine suppressed CCL21-induced bone marrow-derived pDC migration due to Rac 1 inactivation, which was reversed by methyllycaconitine, a JAK2 inhibitor AG490 or caspase-3 inhibitor AZ-10417808. CCL21 was mainly expressed in the isolated lymphoid follicles (ILFs) of the colon during OXZ colitis. The therapeutic effect of cholinergic pathway on OXZ colitis probably through α7nAChRs on pDCs were attributed to the suppression of pDC migration toward the ILFs. Therefore, the activation of α7nAChRs has innovative therapeutic potential for the treatment of UC.

Background Perianal fistula is a disabling complication of Crohn’s disease which greatly impacts quality of life. To address a scarcity of data in Asian populations we determined the prevalence of Crohn’s disease-associated perianal fistula in Japan, the order of diagnosis, and medical history of patients. Methods A retrospective, longitudinal, observational cohort study was conducted, using an employer-based health insurance claims database. The study included patients diagnosed with Crohn’s disease and/or perianal fistula from October 2013 to September 2019. Results The age- and gender-adjusted prevalence rates of Crohn’s disease-associated perianal fistula increased from 10.33 per 100,000 in 2014, to 13.68 per 100,000 in 2019. Among patients with Crohn’s disease-associated perianal fistula, 15.7% were diagnosed with perianal fistula after diagnosis of Crohn’s disease, 68.6% were diagnosed with perianal fistula before diagnosis with Crohn’s disease, and 15.7% were diagnosed with Crohn’s disease and perianal fistula within the same month. Of the patients diagnosed with Crohn’s disease after perianal fistula, approximately 30% were diagnosed with perianal fistula by the age of 20 years, whereas less than 10% of perianal fistula patients without Crohn’s disease were diagnosed with perianal fistula by the age of 20 years. Conclusions The study reveals the prevalence of Crohn’s disease-associated perianal fistula in Japan and that most individuals were diagnosed with Crohn’s disease after the diagnosis of perianal fistula. Crohn’s disease may be underdiagnosed in patients with perianal fistula; patients diagnosed with perianal fistula at a young age should be monitored to allow timely diagnosis of Crohn’s disease.

No abstract

No abstract

No abstract