Expression of TIM-3, Human beta-defensin-2, and FOXP3 and Correlation with Disease Activity in Pediatric Crohn's Disease with Infliximab Therapy.
- Author:
Mi Jin KIM
1
;
Woo Yong LEE
;
Yon Ho CHOE
Author Information
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords: Crohn disease; Infliximab; T-cell immunoglobulin- and mucin-domain-containing molecule 3; forkhead box protein 3; Human beta-defensins-2
- MeSH: Adolescent; Case-Control Studies; Colon/immunology; Crohn Disease/*drug therapy/immunology/*metabolism; Female; Forkhead Transcription Factors/*metabolism; Gastrointestinal Agents/*therapeutic use; Humans; Infliximab/*therapeutic use; Intestinal Mucosa/immunology; Leukocytes, Mononuclear/*metabolism; Male; Membrane Proteins/*metabolism; T-Lymphocytes, Regulatory/immunology; beta-Defensins/*metabolism
- From:Gut and Liver 2015;9(3):370-380
- CountryRepublic of Korea
- Language:English
- Abstract: BACKGROUND/AIMS: This study investigated the expression of T cell immunoglobulin- and mucin-domain-containing molecule 3 (TIM-3), human beta-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. METHODS: We 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. RESULTS: A 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). CONCLUSIONS: Our 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.