Gastroenterology
Volume 132, Issue 3 , Pages 994-1008 , March 2007

Inhibition of TGF-β Signaling by IL-15: A New Role for IL-15 in the Loss of Immune Homeostasis in Celiac Disease

  • Mélika Benahmed

      Affiliations

    • INSERM U793, Paris, France
    • Université Paris Descartes, Faculté de Médecine René Descartes, Paris, France
    • M. Ben Ahmed was supported by INSERM, IRMAD, and AFDIAG (Association Française des Intolérants au Gluten).
  • ,
  • Bertrand Meresse

      Affiliations

    • INSERM U793, Paris, France
    • Université Paris Descartes, Faculté de Médecine René Descartes, Paris, France
  • ,
  • Bertrand Arnulf

      Affiliations

    • Université Paris Descartes, Faculté de Médecine René Descartes, Paris, France
    • CNRS UMR 8147, Paris, France
    • Department of Hematology, AP-HP, Hôpital Necker-Enfants Malades, Paris, France
  • ,
  • Ullah Barbe

      Affiliations

    • INSERM U793, Paris, France
    • Université Paris Descartes, Faculté de Médecine René Descartes, Paris, France
  • ,
  • Jean–Jacques Mention

      Affiliations

    • INSERM U793, Paris, France
    • Université Paris Descartes, Faculté de Médecine René Descartes, Paris, France
  • ,
  • Virginie Verkarre

      Affiliations

    • INSERM U793, Paris, France
    • Université Paris Descartes, Faculté de Médecine René Descartes, Paris, France
    • Department of Pathology, AP-HP, Hôpital Necker-Enfants Malades, Paris, France
  • ,
  • Matthieu Allez

      Affiliations

    • Department of Gastroenterology, AP-HP, Hôpital Saint Louis, Paris, France
  • ,
  • Christophe Cellier

      Affiliations

    • INSERM U793, Paris, France
    • Université Paris Descartes, Faculté de Médecine René Descartes, Paris, France
    • Department of Gastroenterology, AP-HP, Hôpital Européen Georges Pompidou, Paris, France
  • ,
  • Olivier Hermine

      Affiliations

    • Université Paris Descartes, Faculté de Médecine René Descartes, Paris, France
    • CNRS UMR 8147, Paris, France
    • Department of Hematology, AP-HP, Hôpital Necker-Enfants Malades, Paris, France
  • ,
  • Nadine Cerf–Bensussan

      Affiliations

    • INSERM U793, Paris, France
    • Université Paris Descartes, Faculté de Médecine René Descartes, Paris, France
    • Corresponding Author InformationAddress requests for reprints to: Nadine Cerf-Bensussan, MD, PhD, INSERM U793, Faculté de Médecine René Descartes-Paris 5, 156 rue de Vaugirard, 75730 Paris Cedex 15, France. fax: (33) 1-40-61-56-38.

Received 15 November 2005 ,Accepted 27 November 2006.

Title About Type File Size
Supplemental Figure 1

Lack of induction of Smad7 and TGIF by IL-15 in control IEL and LPL. IEL and LPL isolated from controls were left unstimulated or cultured for 5 days with 10 ng/mL of IL-15. TGIF and Smad7 mRNA were quantified by real-time PCR. Results, expressed in arbitrary units, are from 3 independent experiments.

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Supplemental Figure 2

Phospho-c-jun up-regulation induced by IL-15 is not mediated by TNF-α secretion. Peripheral and intestinal T lymphocytes were cultured with medium added or not with IL-15 (10 ng/mL) and/or anti-TNF-α (10 μg/mL) for 5 days. (A) Histogram analysis of intracellular staining of phospho-c-jun in peripheral CD3+ lymphocytes on day 5. (B) Intracellular labeling for TNF-α was monitored every day by flow cytometry in peripheral CD3+ lymphocytes, IEL and LPL. Cells induced with PMA (50 ng/mL) and ionomycin (10−6 M) for 24 hours were used as positive controls. Results, obtained on day 1 and day 5 are shown. Results are representative of 2 independent experiments.

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 This work was sponsored by INSERM, by ARC Grant 4616, Canceropole Ile de France, and by La Fondation Princesse Grace de Monaco.

 The authors are grateful to members of the GERMC and particularly to Pr. M. Lehman (Hôpital Saint Louis), Dr. T. Matysiak-Budnik, Dr. D. Lamarque (Hôpital Hôtel Dieu), Pr. Chaussade (Hôpital Cochin), and Pr. Cugnenc (Hôpital Georges Pompidou) for providing material and information from their patients. The authors thank Dr. D. Buzoni-Gatel for helpful discussions and Mr. G. Pivert for technical support with histology.

PII: S0016-5085(06)02675-8

doi: 10.1053/j.gastro.2006.12.025

Gastroenterology
Volume 132, Issue 3 , Pages 994-1008 , March 2007