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.

Sarra, M., Cupi, M.L., Monteleone, I., Franze, E., Ronchetti, G., Di Sabatino, A., et al. (2013). IL-15 positively regulates IL-21 production in celiac disease mucosa. MUCOSAL IMMUNOLOGY, 6(2), 244-255 [10.1038/mi.2012.65].

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

Sarra M.;Cupi M. L.;Monteleone I.;Franze E.;Gentileschi P.;FRANCESCHILLI, LUANA;Sileri P.;Sica G.;Del Vecchio Blanco G.;CRETELLA, MICAELA;Pallone F.;Monteleone G.
2013

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.
Pubblicato
Rilevanza internazionale
Articolo
Esperti anonimi
Settore MED/18 - Chirurgia Generale
Settore MED/12
English
Con Impact Factor ISI
Celiac Disease; Cells, Cultured; Gene Expression; Humans; Interferon-gamma; Interleukin-15; Interleukins; Intestinal Mucosa; Proto-Oncogene Proteins c-akt; Receptors, Antigen, T-Cell, gamma-delta; Receptors, CXCR5; T-Lymphocyte Subsets
Sarra, M., Cupi, M.L., Monteleone, I., Franze, E., Ronchetti, G., Di Sabatino, A., et al. (2013). IL-15 positively regulates IL-21 production in celiac disease mucosa. MUCOSAL IMMUNOLOGY, 6(2), 244-255 [10.1038/mi.2012.65].
Sarra, M; Cupi, Ml; Monteleone, I; Franze, E; Ronchetti, G; Di Sabatino, A; Gentileschi, P; Franceschilli, L; Sileri, P; Sica, G; Del Vecchio Blanco, G; Cretella, M; Paoluzi, Oa; Corazza, Gr; Pallone, F; Monteleone, G
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2108/197056
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