title: NKT cells are required to induce high IL-33 expression in hepatocytes during ConA-induced acute hepatitis.
abstract: Interleukin-33 (IL-33) is thought to be released during cellular death as an alarming cytokine during the acute phase of disease, but its regulation in vivo is poorly understood. We investigated the expression of IL-33 in two mouse models of acute hepatitis by administering either carbon tetrachloride (CCl(4) ) or concanavalin A (ConA). IL-33 was overexpressed in both models but with a stronger induction in ConA-induced hepatitis. IL-33 was weakly expressed in vascular and sinusoidal endothelial cells from normal liver and was clearly induced in CCl(4) -treated mice. Surprisingly, we found that hepatocytes strongly expressed IL-33 exclusively in the ConA model. CD1d knock-out mice, which are deficient in NKT cells and resistant to ConA-induced hepatitis, no longer expressed IL-33 in hepatocytes following ConA administration. Interestingly, invariant NKT (iNKT) cells adoptively transferred into ConA-treated CD1d KO mouse restored IL-33 expression in hepatocytes. This strongly suggests that NKT cells are responsible for the induction of IL-33 in hepatocytes.
authors.affiliation: Université de Rennes 1, Rennes, France.
authors.forename: Muhammad I
authors.initials: MI
authors.lastname: Arshad
authors.forename: Michel
authors.initials: M
authors.lastname: Rauch
authors.forename: Annie
authors.initials: A
authors.lastname: L'helgoualc'h
authors.forename: Valérie
authors.initials: V
authors.lastname: Julia
authors.forename: Maria C
authors.initials: MC
authors.lastname: Leite-de-Moraes
authors.forename: Catherine
authors.initials: C
authors.lastname: Lucas-Clerc
authors.forename: Claire
authors.initials: C
authors.lastname: Piquet-Pellorce
authors.forename: Michel
authors.initials: M
authors.lastname: Samson
mesh_terms: D000208:Acute Disease; D019264:Adoptive Transfer; D000818:Animals; D055610:Antigens, CD1d / Q000235:genetics / Q000378:metabolism; D002251:Carbon Tetrachloride; D003208:Concanavalin A; D005260:Female; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D015870:Gene Expression; D006520:Hepatitis, Animal / Q000139:chemically induced / Q000235:genetics* / Q000378:metabolism; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D000067596:Interleukin-33; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D007378:Interleukins / Q000235:genetics* / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D055611:Natural Killer T-Cells / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: D055610:Antigens, CD1d; C526879:Cd1d1 protein, mouse; C506535:Il33 protein, mouse; D053583:Interleukin-1beta; D000067596:Interleukin-33; D015850:Interleukin-6; D007378:Interleukins; D014409:Tumor Necrosis Factor-alpha; D003208:Concanavalin A; D002251:Carbon Tetrachloride