Gut Liver.  2015 May;9(3):370-380. 10.5009/gnl13408.

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

• Kim MJ
• Lee WY
• Choe YH

• KMID: 2155645
• DOI: http://doi.org/10.5009/gnl13408

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.

Keyword

Crohn disease; Infliximab; T-cell immunoglobulin- and mucin-domain-containing molecule 3; forkhead box protein 3; Human beta-defensins-2

MeSH Terms

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
Forkhead Transcription Factors
Gastrointestinal Agents
Infliximab
Membrane Proteins
beta-Defensins