Expression of TIM-3, Human β-defensin-2, and FOXP3 and Correlation with Disease Activity in Pediatric Crohn's Disease with Infliximab Therapy

Abstract

Background/AimsThis study investigated the expression of T cell immunoglobulin- and mucin-domain-containing molecule 3 (TIM-3), human β-defensin (HBD)-2, forkhead box protein 3 (FOXP3), and the frequency of CD4+ CD25+ FOXP3+ regulatory T cells (Tregs) in children with Crohn’s disease (CD) during infliximab therapy.MethodsWe enrolled 20 CD patients who received infliximab treatment for 1 year. Peripheral blood and colonic mucosal specimens were collected from all CD patients and from healthy control individuals.ResultsA significant difference in TIM-3 mRNA expression was evident in peripheral blood mononuclear cells and colonic mucosa between CD patients before infliximab therapy and the healthy controls (p<0.001 and p=0.005, respectively). A significant difference in HBD-2 mRNA expression was found in colonic mucosa between CD patients before infliximab therapy and the healthy controls (p=0.013). In the active phase of CD, at baseline, the median percentage of T cells that were CD25+ FOXP3+ was 1.5% (range, 0.32% to 3.49%), which increased after inflixmab treatment for 1 year to 2.2% (range, 0.54% to 5.02%) (p=0.008).ConclusionsOur study suggests that both the adaptive and innate immune systems are closely linked to each other in CD pathogenesis. And the results of our study indicate that it could be a useful therapeutic tool, where restoration of TIM-3, HBD-2 and the function of Tregs may repair the dysfunctional immunoregulation in CD.

Crohn’s Disease Biologic Therapies Advances: A current review

“…Expression of HBD-2 was increased in mucosa of CD patients compared to HC and, after IFX, HBD-2 expression was decreased, due to the decreasing inflammatory stimuli. Therefore, both IS are closely correlated to each other in CD pathogeneses once there was a negative correlation between TIM-3 in PBMC and HBD-2 in the mucosa [1].…”

“…The same response was found in an identical study conducted by Eder P et al Kim MJ. et al suggests that both the innate and adaptive immune system play a key role in the pathogenesis of CD [1]. To reach this conclusion, they studied CD4 + CD35 + FOXP3 + Treg cells and TIM-3, connected to the adaptive system, and the Human β-defences (HBD), linked to the innate system.…”

“…Th1 and Th17 cells undergo apoptosis when galectin 9 (Gal-9), a physiological ligand, connects to T-cell immunoglobulin and mucin-domain-containing molecule 3 (TIM-3), expressed on the membrane of these cells. Regulatory T cells CD4 + CD25 + (Tregs) are essential cells for the maintenance of mucosal tolerance regulated by forkhead box protein 3 (FOXP3) [1].…”

“…Immunological imbalance causes a chronic inflammation in consequence of a dysregulation of innate and adaptive immune response to commensal bacteria in the intestinal mucosa [1].…”

“…The Inflammatory Bowel Disease (IBD) is a group of a chronic condition that includes Crohn's Disease (CD) and ulcerative colitis with unknown ethiology that affects the gastrointestinal tract [1,2]. CD is characterized by segmental granulomatous inflammation with periods of exacerbation and remission [3,4].…”