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

Kim MJ, Lee WY, Choe YH - Gut Liver (2015)

Bottom Line: 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).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.

View Article: PubMed Central - PubMed

Affiliation: Department of Pediatrics, Ilsan Paik Hospital, Inje University College of Medicine, Goyang, Korea.

ABSTRACT

Background/aims: This study investigated the expression of T cell immunoglobulin- and mucin-domain-containing molecule 3 (TIM-3), human β-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.

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Related in: MedlinePlus

CD4+ CD25+ FOXP3+ Tregs in peripheral blood. (A) Representative dot plot of forkhead box protein 3 (FOXP3) and CD25 staining in CD4+ peripheral blood lymphocytes from one patient before and after infliximab therapy (IFX Tx). (B) Comparison of the percentage of CD4+ CD25+ FOXP3+ cells before and after IFX Tx. Box plots define the values for the median, range, and 25th and 75th percentiles. The range is represented by the upper and lower limits of the vertical lines. (C) A nagative correlation of the percentage of CD4+ CD25+ FOXP3+ cells with respect to the Pediatric Crohn’s Disease Activity Index (PCDAI) during IFX Tx (r2=0.604, p<0.001).
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f6-gnl-09-370: CD4+ CD25+ FOXP3+ Tregs in peripheral blood. (A) Representative dot plot of forkhead box protein 3 (FOXP3) and CD25 staining in CD4+ peripheral blood lymphocytes from one patient before and after infliximab therapy (IFX Tx). (B) Comparison of the percentage of CD4+ CD25+ FOXP3+ cells before and after IFX Tx. Box plots define the values for the median, range, and 25th and 75th percentiles. The range is represented by the upper and lower limits of the vertical lines. (C) A nagative correlation of the percentage of CD4+ CD25+ FOXP3+ cells with respect to the Pediatric Crohn’s Disease Activity Index (PCDAI) during IFX Tx (r2=0.604, p<0.001).

Mentions: Representative FACS analysis of FOXP3 and CD25 expression, gated on the CD4+ T cells, by lymphocytes is shown in Fig. 6A. 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 up to 2.2% (range, 0.54% to 5.02%) (p=0.008) (Fig. 6B). The change in disease activity, measured as PCDAI during inflixmab therapy was inversely correlated with the upregulation of CD25+ FOXP3+ Tregs (r2=0.604, p<0.001) (Fig. 6C).


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

Kim MJ, Lee WY, Choe YH - Gut Liver (2015)

CD4+ CD25+ FOXP3+ Tregs in peripheral blood. (A) Representative dot plot of forkhead box protein 3 (FOXP3) and CD25 staining in CD4+ peripheral blood lymphocytes from one patient before and after infliximab therapy (IFX Tx). (B) Comparison of the percentage of CD4+ CD25+ FOXP3+ cells before and after IFX Tx. Box plots define the values for the median, range, and 25th and 75th percentiles. The range is represented by the upper and lower limits of the vertical lines. (C) A nagative correlation of the percentage of CD4+ CD25+ FOXP3+ cells with respect to the Pediatric Crohn’s Disease Activity Index (PCDAI) during IFX Tx (r2=0.604, p<0.001).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4413971&req=5

f6-gnl-09-370: CD4+ CD25+ FOXP3+ Tregs in peripheral blood. (A) Representative dot plot of forkhead box protein 3 (FOXP3) and CD25 staining in CD4+ peripheral blood lymphocytes from one patient before and after infliximab therapy (IFX Tx). (B) Comparison of the percentage of CD4+ CD25+ FOXP3+ cells before and after IFX Tx. Box plots define the values for the median, range, and 25th and 75th percentiles. The range is represented by the upper and lower limits of the vertical lines. (C) A nagative correlation of the percentage of CD4+ CD25+ FOXP3+ cells with respect to the Pediatric Crohn’s Disease Activity Index (PCDAI) during IFX Tx (r2=0.604, p<0.001).
Mentions: Representative FACS analysis of FOXP3 and CD25 expression, gated on the CD4+ T cells, by lymphocytes is shown in Fig. 6A. 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 up to 2.2% (range, 0.54% to 5.02%) (p=0.008) (Fig. 6B). The change in disease activity, measured as PCDAI during inflixmab therapy was inversely correlated with the upregulation of CD25+ FOXP3+ Tregs (r2=0.604, p<0.001) (Fig. 6C).

Bottom Line: 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).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.

View Article: PubMed Central - PubMed

Affiliation: Department of Pediatrics, Ilsan Paik Hospital, Inje University College of Medicine, Goyang, Korea.

ABSTRACT

Background/aims: This study investigated the expression of T cell immunoglobulin- and mucin-domain-containing molecule 3 (TIM-3), human β-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.

Show MeSH
Related in: MedlinePlus