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Abstract Title:

IL-15 positively regulates IL-21 production in celiac disease mucosa.

Abstract Source:

Mucosal Immunol. 2012 Jul 11. Epub 2012 Jul 11. PMID: 22785229

Abstract Author(s):

M Sarra, M L Cupi, I Monteleone, E Franzè, G Ronchetti, A Di Sabatino, P Gentileschi, L Franceschilli, P Sileri, G Sica, G Del Vecchio Blanco, M Cretella, O A Paoluzi, G R Corazza, F Pallone, G Monteleone

Article Affiliation:

Department of Internal Medicine, University"Tor Vergata"of Rome, Rome, Italy.

Abstract:

Celiac disease (CD)-associated inflammation is characterized by high interleukin- 21 (IL-21), but the mechanisms that control IL-21 production are not fully understood. Here we analyzed IL-21 cell sources and examined how IL-21 production is regulated in CD. Intraepithelial lymphocytes (IELs) and lamina propria lymphocytes (LPLs), isolated from CD patients and non-CD controls, were analyzed for cell markers, cytokines, and transcription factors by flow cytometry. IL-21 was highly produced by CD4+ and CD4+/CD8+ IELs and LPLs in active CD. IL-21-producing cells coexpressed interferon-γ (IFN-γ) and to a lesser extent T helper type 17 (Th17) cytokines. Treatment of control LPLs with IL-15, a cytokine overproduced in CD, activated Akt and STAT3 (signal transducer and activator of transcription 3), thus enhancing IL-21 synthesis. Active CD biopsies contained elevated levels of Akt, and blockade of IL-15 in those samples reduced IL-21. Similarly, neutralization of IL-15 in biopsies of inactive CD patients inhibited peptic-tryptic digest of gliadin-induced IL-21 expression. These findings indicate that in CD, IL-15 positively regulates IL-21 production.Mucosal Immunology advance online publication 11 July 2012. doi:10.1038/mi.2012.65.

Study Type : Review
Additional Links
Problem Substances : Gliadin : CK(819) : AC(116)

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