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

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

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Pages (from-to)244-255
Number of pages12
JournalMucosal Immunology
Issue number2
Publication statusPublished - Mar 2013

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy


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