Celiac disease (CD) is a gluten-sensitive enteropathy associated with a marked infiltration of the mucosa with IFN-gamma-secreting Th1 cells. Recent studies have shown that a novel subset of T cells characterized by expression of high levels of IL-17A, termed Th17 cells, may be responsible for pathogenic effects previously attributed to Th1 cells. In this study, we characterized the expression of IL-17A-producing cells in CD. By real-time PCR and ELISA, it was shown that expression of IL-17A RNA and protein is more pronounced in active CD biopsy specimens in comparison with inactive CD and normal mucosal biopsy specimens. Flow cytometry confirmed that IL-17A is overproduced in CD mucosa and that CD4(+) and CD4(+)CD8(+) cells were major sources. The majority of IL-17A-producing CD4(+) and CD4(+)CD8(+) cells coexpressed IFN-gamma but not CD161. The addition of a peptic-tryptic digest of gliadin to ex vivo organ cultures of duodenal biopsy specimens taken from inactive CD patients enhanced IL-17A production by both CD4(+) and CD4(+)CD8(+) cells. Because we previously showed that IL-21, a T cell-derived cytokine involved in the control of Th17 cell responses, is overproduced in CD, we next assessed whether IL-17A expression is regulated by IL-21. Blockade of IL-21 activity by a neutralizing IL-21 Ab reduced IL-17A expression in cultures of active CD and peptic-tryptic digest of gliadin-treated CD biopsy specimens. In conclusion, our data show that IL-17A is increased in CD and is produced by cells that also make IFN-gamma.

Monteleone, I., Sarra, M., DEL VECCHIO BLANCO, G., Paoluzi, O., Franzè, E., Fina, D., et al. (2010). Characterization of IL-17A-producing cells in celiac disease mucosa. JOURNAL OF IMMUNOLOGY, 184(4), 2211-2218 [10.4049/jimmunol.0901919].

Characterization of IL-17A-producing cells in celiac disease mucosa

MONTELEONE, IVAN;DEL VECCHIO BLANCO, GIOVANNA;PALLONE, FRANCESCO;MONTELEONE, GIOVANNI
2010-02-15

Abstract

Celiac disease (CD) is a gluten-sensitive enteropathy associated with a marked infiltration of the mucosa with IFN-gamma-secreting Th1 cells. Recent studies have shown that a novel subset of T cells characterized by expression of high levels of IL-17A, termed Th17 cells, may be responsible for pathogenic effects previously attributed to Th1 cells. In this study, we characterized the expression of IL-17A-producing cells in CD. By real-time PCR and ELISA, it was shown that expression of IL-17A RNA and protein is more pronounced in active CD biopsy specimens in comparison with inactive CD and normal mucosal biopsy specimens. Flow cytometry confirmed that IL-17A is overproduced in CD mucosa and that CD4(+) and CD4(+)CD8(+) cells were major sources. The majority of IL-17A-producing CD4(+) and CD4(+)CD8(+) cells coexpressed IFN-gamma but not CD161. The addition of a peptic-tryptic digest of gliadin to ex vivo organ cultures of duodenal biopsy specimens taken from inactive CD patients enhanced IL-17A production by both CD4(+) and CD4(+)CD8(+) cells. Because we previously showed that IL-21, a T cell-derived cytokine involved in the control of Th17 cell responses, is overproduced in CD, we next assessed whether IL-17A expression is regulated by IL-21. Blockade of IL-21 activity by a neutralizing IL-21 Ab reduced IL-17A expression in cultures of active CD and peptic-tryptic digest of gliadin-treated CD biopsy specimens. In conclusion, our data show that IL-17A is increased in CD and is produced by cells that also make IFN-gamma.
15-feb-2010
Pubblicato
Rilevanza internazionale
Articolo
Sì, ma tipo non specificato
Settore MED/12 - GASTROENTEROLOGIA
English
Con Impact Factor ISI
Intestinal mucosa; celiac disease; interleukins; cd8-positive t-lymphocytes; interferon-gamma; humans; inflammation mediators; organ culture techniques; up-regulation; duodenum; gene expression regulation; cd4-positive t-lymphocytes; interleukin-17
Monteleone, I., Sarra, M., DEL VECCHIO BLANCO, G., Paoluzi, O., Franzè, E., Fina, D., et al. (2010). Characterization of IL-17A-producing cells in celiac disease mucosa. JOURNAL OF IMMUNOLOGY, 184(4), 2211-2218 [10.4049/jimmunol.0901919].
Monteleone, I; Sarra, M; DEL VECCHIO BLANCO, G; Paoluzi, O; Franzè, E; Fina, D; Fabrizi, A; Macdonald, T; Pallone, F; Monteleone, G
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/23078
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