Korean J Pediatr Gastroenterol Nutr.  2011 Sep;14(3):258-268. 10.5223/kjpgn.2011.14.3.258.

FOXP3+T Cells and TGF-beta1 in Colonic Mucosa of Children with Crohn's Disease

• Gil JH
• Oh JE
• Seo JW
• Cho MS
• Cho KY
• Yoo ES

• KMID: 2276885
• DOI: http://doi.org/10.5223/kjpgn.2011.14.3.258

Abstract

PURPOSE
Forkhead box protein 3 (FOXP3)+T cells are the major regulatory T cells controlling all aspects of the immune response. Transforming growth factor-beta (TGF-beta) is a suppressive cytokine which mediates the suppressive action of FOXP3+T cells. The aim of this study was to investigate the role of FOXP3+T cells, TGF-beta in colonic mucosa of children with Crohn's disease (CD).
METHODS
Colonic mucosal biopsies were obtained from 10 children with CD (12~15 years of age) and 11 control (8~15 years of age). Frequencies of FOXP3+T, CD4+T cells and TGF-beta1 expression were examined in the lamina propria (LP) and lymphoid aggregates or follicles (LA/F) by immunohistochemistry, and later evaluated by association with disease activity.
RESULTS
In the LP of CD group, frequencies of FOXP3+T, CD4+T cells, proportion of FOXP3/CD4+T cells and TGF-beta1 expression significantly increased compared to the control. In the LA/F of CD group, frequency of FOXP3+T cells, proportion of FOXP3/CD4+T cells and TGF-beta1 expression significantly increased compared to the control (p<0.05). CD4+T cells also increased compared to the control, but this finding was not significant. In the LP and LA/F of CD group, frequency of FOXP3+T cells exhibited positive correlation with CD4+T cells (p<0.05). In the LP and LA/F of CD group, TGF-beta1 expression had positive correlation with CRP, Pediatric Crohn's Disease Activity Index, and negative correlation with hematocrit and albumin (p<0.05).
CONCLUSION
Increased frequency of FOXP3+T cells and TGF-beta1 expression in colonic mucosa of CD can be interpreted as a compensatory increase towards achieving down-regulation of immune responses.

Keyword

T-lymphocytes; Regulatory; Crohn's disease; FOXP3; CD4; Transforming growth factor beta; Child; Disease activity

MeSH Terms

Biopsy
Child
Colon
Crohn Disease
Down-Regulation
Hematocrit
Humans
Immunohistochemistry
Mucous Membrane
T-Lymphocytes
T-Lymphocytes, Regulatory
Transforming Growth Factor beta
Transforming Growth Factor beta1
Crohn Disease
Transforming Growth Factor beta
Transforming Growth Factor beta1

Figure

• 

  Fig. 1 Immunohistochemical staining of FOXP3 (×400). (A) In the lamina propria (LP) of Crohn's disease (CD) group. (B) In the LP of the control. (C) In the lymphoid aggregates or follicles (LA/F) of CD group. (D) In the LA/F of the control.

• 

  Fig. 2 Immunohistochemical staining of CD4 (×400). (A) In the LP of CD group. (B) In the LP of the control. (C) In the LA/F of CD group. (D) In the LA/F of the control.

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  Fig. 3 Immunohistochemical staining of TGF-β1 (×400). (A) Grade 0 in the control, (B) Grade 1, (C) Grade 2, (D) Grade 3 in CD group.

• 

  Fig. 4 The frequencies of FOXP3+T, CD4+T cells, and the proportion of FOXP3+T cells to CD4+T cells and TGF-β1 expression were more increased in the lamina propria of Crohn's disease group (n=10) than the control (n=11). (A) FOXP3+T cells, (B) CD4+T cells, (C) FOXP3/CD4+T cells, (D) TGF-β1 expression.

• 

  Fig. 5 The frequencies of FOXP3+T, CD4+T cells, and the proportion of FOXP3+T cells to CD4+T cells and TGF-β1 expression were more increased in the lymphoid aggregates or follicles of Crohn's disease group (n=8) than the control (n=10). (A) FOXP3+T cells, (B) CD4+T cells, (C) FOXP3/CD4+T cells, (D) TGF-β1 expression.

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