IL-15 modulates the effect of retinoic acid, promoting inflammation rather than oral tolerance to dietary antigens

Abstract

Evaluation of: DePaolo RW, Abadie V, Tang F et al. Co-adjuvant effects of retinoic acid and IL-15 induce inflammatory immunity to dietary antigens. Nature 471(7337), 220–224 (2011).

The physiological immune response in the intestine against dietary proteins and commensal flora is characterized by regulatory mechanisms (tolerance) that prevent harmful consequences. Intestinal dendritic cells (DCs) have a central role in the development of immunosuppressive regulatory T cells owing to their ability to produce TGF-β and retinoic acid (RA). However, the article under evaluation shows an unexpected effect of RA – that of promoting a proinflammatory phenotype in intestinal DCs involved in the generation of inflammatory immune responses to dietary antigens. By using a double transgenic murine model that resembles human celiac disease, it was demonstrated that RA synergizes with IL-15 in promoting the breakdown of gluten tolerance and the development of enteropathy. The tissue microenvironment modulates DC function, and immune therapies that are based on RA aiming to restore oral tolerance should be used with caution because the presence of IL-15 (and/or other proinflammatory cytokines) may have undesirable effects.

Keywords::

• celiac disease
• dietary antigens
• IL-15
• inflammation
• intestine
• retinoic acid
• tolerance

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.