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Characterization of IL-17A-Producing Cells in Celiac Disease Mucosa

Celiac.com 02/03/2010 - Celiac disease increases production of IL-17A by cells that also make IFN-gamma. Recently, a research team set out to characterize the expression of IL-17A-producing cells in celiac disease.

The team included I. Monteleone, M. Sarra, G. Del Vecchio Blanco, O. A. Paoluzi, E. Franzè, D. Fina, A. Fabrizi, T. T. Macdonald, F. Pallone, and G. Monteleone of the Department of Internal Medicine at the University of Tor Vergata in Rome, Italy.

Infiltration of the mucosa with IFN-gamma-secreting Th1 cells is one of the features associated with celiac disease. Recent studies have shown the pathogenic effects previously attributed to Th1 cells may in fact be caused by a novel subset of T cells, termed Th17 cells, and noted for expressing high levels of IL-17A.

In this study, the team set out to characterize the expression of IL-17A-producing cells in celiac disease. Using real-time PCR and ELISA, the team showed that expression of IL-17A RNA and protein is greater in active celiac disease biopsy specimens than in specimens from inactive celiac disease, and normal mucosal biopsies.

Through flow cytometry, the team confirmed that the mucosa of celiac disease patients overproduces IL-17A, and that the main sources for this overproduction were CD4(+) and CD4(+)CD8(+) cells.  Most IL-17A-producing CD4(+) and CD4(+)CD8(+) cells co-expressed IFN-gamma but did not co-express CD161.

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Including a peptic-tryptic digest of gliadin to ex-vivo organ cultures of duodenal biopsy specimens taken from patients with inactive celiac disease enhanced IL-17A production 
by both CD4(+) and CD4(+)CD8(+) cells.

Since the team showed earlier that patients with celiac disease overproduced IL-21, a T cell-derived cytokine involved in the control of Th17 cell responses, they next determined whether IL-21 was responsible for regulating IL-17A expression.

Blocking IL-21 action with a neutralizing IL-21 Ab lowered total IL-17A expression in cultures of active celiac disease and peptic-tryptic digest of gliadin-treated celiac disease biopsy specimens.

From the data, the team concludes that celiac disease increases IL-17A, which is produced by cells that also produce IFN-gamma.

Source: Journal of Immunology, 2010 Jan 8.

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