title: Exosome-like nanoparticles from intestinal mucosal cells carry prostaglandin E2 and suppress activation of liver NKT cells.
abstract: 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 PGE2, 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' PGE2. Blocking PGE2 synthesis attenuated IDENs inhibition of induction of IFN-γ and IL-4 by α-galactosylceramide (α-GalCer)-stimulated liver NKT cells in a PGE2 E-type prostanoid 2/E-type prostanoid 4 receptor-mediated manner. Proinflammatory conditions enhanced the migration of IDENs to the liver where α-GalCer and PGE2 induced NKT anergy in response to subsequent α-GalCer stimulation. These findings demonstrate that IDENs carrying PGE2 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.
authors.affiliation: Department of Microbiology and Immunology, Brown Cancer Center, University of Louisville, Louisville, KY 40202, USA.
authors.forename: Zhong-Bin
authors.initials: ZB
authors.lastname: Deng
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Zhuang
authors.forename: Songwen
authors.initials: S
authors.lastname: Ju
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Xiang
authors.forename: Jingyao
authors.initials: J
authors.lastname: Mu
authors.forename: Yuelong
authors.initials: Y
authors.lastname: Liu
authors.forename: Hong
authors.initials: H
authors.lastname: Jiang
authors.forename: Lifeng
authors.initials: L
authors.lastname: Zhang
authors.forename: James
authors.initials: J
authors.lastname: Mobley
authors.forename: Craig
authors.initials: C
authors.lastname: McClain
authors.forename: Wenke
authors.initials: W
authors.lastname: Feng
authors.forename: William
authors.initials: W
authors.lastname: Grizzle
authors.forename: Jun
authors.initials: J
authors.lastname: Yan
authors.forename: Donald
authors.initials: D
authors.lastname: Miller
authors.forename: Mitchell
authors.initials: M
authors.lastname: Kronenberg
authors.forename: Huang-Ge
authors.initials: HG
authors.lastname: Zhang
mesh_terms: D000818:Animals; D055252:Cell-Derived Microparticles / Q000378:metabolism*; D017635:Clonal Anergy / Q000276:immunology; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism*; D004195:Disease Models, Animal; D055354:Exosomes / Q000276:immunology / Q000378:metabolism*; D005699:Galactosylceramides / Q000276:immunology; D019693:Hepatitis, Autoimmune / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007413:Intestinal Mucosa / Q000276:immunology / Q000378:metabolism*; D008099:Liver / Q000276:immunology* / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology*; D008297:Male; D051379:Mice; D055611:Natural Killer T-Cells / Q000276:immunology*; D015398:Signal Transduction
chemical_list: D005699:Galactosylceramides; C493154:alpha-galactosylceramide; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D015232:Dinoprostone