Exosome-like Nanoparticles from Intestinal Mucosal Cells Carry Prostaglandin E2 and Suppress Activation of Liver NKT Cells

Regulation and induction of anergy in NKT cells of the liver can inhibit autoimmune and antitumor responses by mechanisms that are poorly understood. We investigated the effects of PGE(2), delivered by intestinal, mucus-derived, exosome-like nanoparticles (IDENs), on NKT cells in mice. In this study, we demonstrate that IDENs migrate to the liver where they induce NKT cell anergy. These effects were mediated by an IDENs' PGE(2). Blocking PGE(2) synthesis attenuated IDENs inhibition of induction of IFN-gamma and IL-4 by alpha-galactosylceramide (alpha-GalCer)-stimulated liver NKT cells in a PGE(2) E-type prostanoid 2/E-type prostanoid 4 receptor-mediated manner. Proinflammatory conditions enhanced the migration of IDENs to the liver where alpha-GalCer and PGE(2) induced NKT anergy in response to subsequent alpha-GalCer stimulation. These findings demonstrate that IDENs carrying PGE(2) can be transferred from the intestine to the liver, where they act as immune modulators, inducing an anergic-like state of NKT cells. These reagents might be developed as therapeutics for autoimmune liver diseases. The Journal of Immunology, 2013, 190: 3579-3589.