Infiltration of forkhead box P3-expressing cells in small intestinal mucosa in coeliac disease but not in type 1 diabetes

Clin Exp Immunol. 2008 Jun;152(3):498-507. doi: 10.1111/j.1365-2249.2008.03662.x. Epub 2008 Apr 24.

Abstract

Because the role of regulatory T cells in the intestinal inflammation is unknown in coeliac disease (CD) and type 1 diabetes (T1D), the expression of forkhead box P3 (FoxP3), CD25, transforming growth factor-beta, interferon (IFN)-gamma, interleukin (IL)-4, IL-8, IL-10, IL-15 and IL-18 was measured by quantitative reverse transcription-polymerase chain reaction in the small intestinal biopsies from paediatric patients with active or potential CD, T1D and control patients. The numbers of FoxP3- and CD25-expressing cells were studied with immunohistochemistry. Enhanced intestinal expressions of FoxP3, IL-10 and IFN-gamma mRNAs were found in active CD when compared with controls (P-values < 0.001, 0.004, <0.001). In potential CD, only the expression of IFN-gamma mRNA was increased. The numbers of FoxP3-expressing cells were higher in active and potential CD (P < 0.001, P = 0.05), and the ratio of FoxP3 mRNA to the number of FoxP3-positive cells was decreased in potential CD when compared with controls (P = 0.007). The ratio of IFN-gamma to FoxP3-specific mRNA was increased in active and potential CD (P = 0.001 and P = 0.002). Patients with T1D had no changes in regulatory T cell markers, but showed increased expression of IL-18 mRNA. The impaired up-regulation of FoxP3 transcripts despite the infiltration of FoxP3-positive cells in potential CD may contribute to the persistence of inflammation. The increased ratio of IFN-gamma to FoxP3 mRNA in active and potential CD suggests an imbalance between regulatory and effector mechanisms. The increased intestinal expression of IL-18 mRNA in patients with T1D adds evidence in favour of the hypothesis that T1D is associated with derangements in the gut immune system.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Celiac Disease / immunology*
  • Child
  • Child, Preschool
  • Cytokines / biosynthesis
  • Cytokines / genetics
  • Diabetes Mellitus, Type 1 / immunology*
  • Female
  • Forkhead Transcription Factors / genetics
  • Forkhead Transcription Factors / metabolism*
  • Humans
  • Immunity, Mucosal
  • Immunoenzyme Techniques
  • Infant
  • Interferon-gamma / biosynthesis
  • Interferon-gamma / genetics
  • Interleukin-2 Receptor alpha Subunit / metabolism
  • Intestinal Mucosa / immunology*
  • Intestine, Small / immunology*
  • Male
  • RNA, Messenger / genetics
  • Reverse Transcriptase Polymerase Chain Reaction / methods
  • T-Lymphocytes, Regulatory / immunology

Substances

  • Cytokines
  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • Interleukin-2 Receptor alpha Subunit
  • RNA, Messenger
  • Interferon-gamma