Co-adjuvant effects of retinoic acid and IL-15 induce inflammatory immunity to dietary antigens

R. W. Depaolo, V. Abadie, F. Tang, H. Fehlner-Peach, J. A. Hall, W. Wang, E. V. Marietta, D. D. Kasarda, T. A. Waldmann, J. A. Murray, C. Semrad, S. S. Kupfer, Y. Belkaid, S. Guandalini, B. Jabri

Research output: Contribution to journalArticle

275 Scopus citations

Abstract

Under physiological conditions the gut-associated lymphoid tissues not only prevent the induction of a local inflammatory immune response, but also induce systemic tolerance to fed antigens. A notable exception is coeliac disease, where genetically susceptible individuals expressing human leukocyte antigen (HLA) HLA-DQ2 or HLA-DQ8 molecules develop inflammatory T-cell and antibody responses against dietary gluten, a protein present in wheat. The mechanisms underlying this dysregulated mucosal immune response to a soluble antigen have not been identified. Retinoic acid, a metabolite of vitamin A, has been shown to have a critical role in the induction of intestinal regulatory responses. Here we find in mice that in conjunction with IL-15, a cytokine greatly upregulated in the gut of coeliac disease patients, retinoic acid rapidly activates dendritic cells to induce JNK (also known as MAPK8) phosphorylation and release the proinflammatory cytokines IL-12p70 and IL-23. As a result, in a stressed intestinal environment, retinoic acid acted as an adjuvant that promoted rather than prevented inflammatory cellular and humoral responses to fed antigen. Altogether, these findings reveal an unexpected role for retinoic acid and IL-15 in the abrogation of tolerance to dietary antigens.

Original languageEnglish (US)
Pages (from-to)220-225
Number of pages6
JournalNature
Volume471
Issue number7337
DOIs
StatePublished - Mar 10 2011

ASJC Scopus subject areas

  • General

Fingerprint Dive into the research topics of 'Co-adjuvant effects of retinoic acid and IL-15 induce inflammatory immunity to dietary antigens'. Together they form a unique fingerprint.

  • Cite this

    Depaolo, R. W., Abadie, V., Tang, F., Fehlner-Peach, H., Hall, J. A., Wang, W., Marietta, E. V., Kasarda, D. D., Waldmann, T. A., Murray, J. A., Semrad, C., Kupfer, S. S., Belkaid, Y., Guandalini, S., & Jabri, B. (2011). Co-adjuvant effects of retinoic acid and IL-15 induce inflammatory immunity to dietary antigens. Nature, 471(7337), 220-225. https://doi.org/10.1038/nature09849