Increased Expression Of T Cell Immunoglobulin And Mucin Domain 3 On Mast Cells Positively Correlates With Abdominal Pain In Irritable Bowel Syndrome

ObjectiveT cell immunoglobulin and mucin-domain containing protein-3(Tim-3)is a novel immunoregulatory gene which has been found on a variety of cell surfaces.The expression of tim-3 on mast cells could influence cytokine production,and degranulation of these cells in vitro.The aim of the study was to investigate the expression of Tim-3 in mucosal mast cells in patients with irritable bowel syndrome(IBS)and its role in the pathogenesis of IBS.The relationship will be analyzed between Tim-3 and visceral hypersensitivity(severe abdominal pain severity and frequency of seizures)in patients with irritable bowel(IBS).The activation of mast cells mediated by Tim-3 may be a potential mechanism for visceral hypersensitivity reactions in IBS.MethodsAccording to the Rome III diagnostic criteria of IBS,26 eligible IBS patients were enrolled in the study,and completed the questionnaire about the abdominal pain symptom score.Thirty IBS patients and 21 healthy controls(HCs)were tested for Tim-3 expression on mast cells in colonic mucosa by flow cytometry.Abdominal pain was quantified by a validated questionnaire.And the relationship between the expression of Tim-3 on mast cells and the severity or frequency of abdominal pain was analyzed with Spearman correlation analysis method.Results1.Compared with HCs,the number of mast cells in the colonic mucosa of IBS patients increased significantly,and the difference was statistically significant.(P < 0.05;Fig.1A and 1B).2.The proportion of Tim-3 positive mast cells in the colonic mucosa of patients with IBS was significantly higher than that of HCs(P < 0.05;Figure 1A and1 C).3.There was a significant positive correlation between the proportion of colonic mucosal mast cells and the severity and frequency of abdominal pain(r = 0.5262,P = 0.0058 and r = 0.4239,respectively,P = 0.0309)(Fig.2A).4.The proportion of mast cells expressing Tim-3 in the colonic mucosa was positively correlated with the severity and frequency of abdominal pain(r = 0.5651,P = 0.0026 and r = 0.4233,respectively,P = 0.0312)(Fig.2B).Conclusion1.According to the increased number of mast cells and the positively relationship between the mast cells and abdominal pain,we could verify that mast cells have participated in the pathogenesis of IBS and is associated with IBS-like visceral hypersensitivity.2.The higher expression of Tim-3 on mast cells in D-IBS patients suggesting that Tim-3 may play a key role in the pathogenesis of D-IBS.It could be speculated that Tim-3 could participate in the pathogenesis of visceral hypersensitivity in IBS by promoting mast cells activation and degranulation.3.Finally,the positively correlationship between expression of Tim-3 on mast cells and abdominal pain suggesting that Tim-3 may be a potential treatment target for IBS.A better understanding of this pathway may shed new light on the pathogenesis of this disease.