Increased FOXP3 expression in small-bowel mucosa of children with coeliac disease and type I diabetes mellitus

Scand J Gastroenterol. 2009;44(4):422-30. doi: 10.1080/00365520802624177.

Abstract

Objective: To determine whether the expression of FOXP3 is changed in small-bowel mucosa in coeliac disease (CD).

Material and methods: The study comprised 52 patients (mean age 8.01+/-6.14 years) who had undergone small-bowel biopsies. CD only was diagnosed in 16 patients, and CD with type I diabetes mellitus (T1D) in 7. These 23 patients and 4 others without CD had partial or subtotal villous atrophy (PVA, SVA). Twenty-five persons without CD had normal mucosa. The transcription level of the FOXP3 gene (Hs00203958_m1) was evaluated in biopsy samples (small bowel) using TaqMan gene expression assays. FOXP3 protein in mucosal cells was evaluated with mouse anti-human FOXP3 antibodies and CD25(+), and CD4(+) T cells were evaluated by mouse monoclonal antibodies.

Results: Expression of FOXP3 mRNA was higher in both PVA and SVA compared to normal mucosa (p=0.007). Patients with CD and T1D had higher expression of FOXP3 mRNA than patients with CD alone (p=0.02). The number of FOXP3(+) cells in intestinal mucosa was higher in patients with CD, especially those with coexisting T1D, than in those with normal mucosa (p=0.01). The results of double staining showed that, among all positive cells, FOXP3 expression alone was revealed in 25.6% of the cells, CD25 positivity in 18% and both markers simultaneously were found in 56.5% of lymphocytes (p=0.03). Double staining for CD4 and FOXP3 showed that 87.5% of cells were CD4(+), 2.8% were FOXP3(+) and 9.7% of cells simultaneously expressed the CD4 and FOXP3 markers.

Conclusions: A more pronounced expression of FOXP3 mRNA and also the number of FOXP3(+) cells (with simultaneous expression of CD25 and CD4 markers) were found in the small-bowel biopsy specimens obtained from children with CD, particularly those with coexisting T1D, compared with the FOXP3 expression in normal mucosa.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • CD4 Antigens / metabolism
  • Case-Control Studies
  • Celiac Disease / complications*
  • Celiac Disease / genetics
  • Celiac Disease / metabolism*
  • Child
  • Child, Preschool
  • Diabetes Mellitus, Type 1 / complications
  • Diabetes Mellitus, Type 1 / genetics
  • Diabetes Mellitus, Type 1 / metabolism*
  • Female
  • Forkhead Transcription Factors / genetics
  • Forkhead Transcription Factors / metabolism*
  • Humans
  • Infant
  • Interleukin-2 Receptor alpha Subunit / metabolism
  • Intestinal Mucosa / metabolism*
  • Intestinal Mucosa / pathology
  • Intestine, Small / metabolism*
  • Intestine, Small / pathology
  • Male
  • RNA, Messenger / metabolism
  • T-Lymphocytes, Regulatory / physiology
  • Young Adult

Substances

  • CD4 Antigens
  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • Interleukin-2 Receptor alpha Subunit
  • RNA, Messenger