title: Interleukin-12 and -23 Control Plasticity of CD127(+) Group 1 and Group 3 Innate Lymphoid Cells in the Intestinal Lamina Propria.
abstract: Human group 1 ILCs consist of at least three phenotypically distinct subsets, including NK cells, CD127(+) ILC1, and intraepithelial CD103(+) ILC1. In inflamed intestinal tissues from Crohn's disease patients, numbers of CD127(+) ILC1 increased at the cost of ILC3. Here we found that differentiation of ILC3 to CD127(+) ILC1 is reversible in vitro and in vivo. CD127(+) ILC1 differentiated to ILC3 in the presence of interleukin-2 (IL-2), IL-23, and IL-1β dependent on the transcription factor RORγt, and this process was enhanced in the presence of retinoic acid. Furthermore, we observed in resection specimen from Crohn's disease patients a higher proportion of CD14(+) dendritic cells (DC), which in vitro promoted polarization from ILC3 to CD127(+) ILC1. In contrast, CD14(-) DCs promoted differentiation from CD127(+) ILC1 toward ILC3. These observations suggest that environmental cues determine the composition, function, and phenotype of CD127(+) ILC1 and ILC3 in the gut.
authors.affiliation: Department of Cell Biology and Histology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands.
authors.forename: Jochem H
authors.initials: JH
authors.lastname: Bernink
authors.affiliation: Department of Cell Biology and Histology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands.
authors.forename: Lisette
authors.initials: L
authors.lastname: Krabbendam
authors.affiliation: Department of Cell Biology and Histology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands.
authors.forename: Kristine
authors.initials: K
authors.lastname: Germar
authors.affiliation: Department of Cell Biology and Histology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands.
authors.forename: Esther
authors.initials: E
authors.lastname: de Jong
authors.affiliation: Research Center Immunology and Institute of Medical Microbiology and Hygiene, University of Mainz Medical Centre, Obere Zahlbacher Strasse 67 D-55131 Mainz, Germany.
authors.forename: Konrad
authors.initials: K
authors.lastname: Gronke
authors.affiliation: Research Center Immunology and Institute of Medical Microbiology and Hygiene, University of Mainz Medical Centre, Obere Zahlbacher Strasse 67 D-55131 Mainz, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Kofoed-Nielsen
authors.affiliation: Department of Hematology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands.
authors.forename: J Marius
authors.initials: JM
authors.lastname: Munneke
authors.affiliation: Department of Hematology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands.
authors.forename: Mette D
authors.initials: MD
authors.lastname: Hazenberg
authors.affiliation: Department of Medical Microbiology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands.
authors.forename: Julien
authors.initials: J
authors.lastname: Villaudy
authors.affiliation: Department of Surgery, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands.
authors.forename: Christianne J
authors.initials: CJ
authors.lastname: Buskens
authors.affiliation: Department of Surgery, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands.
authors.forename: Willem A
authors.initials: WA
authors.lastname: Bemelman
authors.affiliation: Research Center Immunology and Institute of Medical Microbiology and Hygiene, University of Mainz Medical Centre, Obere Zahlbacher Strasse 67 D-55131 Mainz, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Diefenbach
authors.affiliation: Department of Cell Biology and Histology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands.
authors.forename: Bianca
authors.initials: B
authors.lastname: Blom
authors.affiliation: Department of Cell Biology and Histology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands. Electronic address: hergen.spits@amc.uva.nl.
authors.forename: Hergen
authors.initials: H
authors.lastname: Spits
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000276:immunology; D002478:Cells, Cultured; D003424:Crohn Disease / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology; D006801:Humans; D053765:Interleukin-12 Subunit p35 / Q000276:immunology*; D053583:Interleukin-1beta / Q000276:immunology; D007376:Interleukin-2 / Q000276:immunology; D053760:Interleukin-23 Subunit p19 / Q000276:immunology*; D053699:Interleukin-7 Receptor alpha Subunit / Q000276:immunology*; D007413:Intestinal Mucosa / Q000166:cytology / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology; D018950:Lipopolysaccharide Receptors / Q000276:immunology; D017710:Lymphocyte Transfusion; D008214:Lymphocytes / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D018345:Mice, Knockout; D016513:Mice, SCID; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3 / Q000276:immunology; D018168:Receptors, Retinoic Acid / Q000378:metabolism; D000072482:Retinoic Acid Receptor alpha; D047491:Retinoid X Receptor gamma / Q000378:metabolism; D014212:Tretinoin / Q000494:pharmacology; D000097768:Retinoic Acid Receptor gamma
chemical_list: D053765:Interleukin-12 Subunit p35; D053583:Interleukin-1beta; D007376:Interleukin-2; D053760:Interleukin-23 Subunit p19; D053699:Interleukin-7 Receptor alpha Subunit; D018950:Lipopolysaccharide Receptors; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D018168:Receptors, Retinoic Acid; D000072482:Retinoic Acid Receptor alpha; D047491:Retinoid X Receptor gamma; D014212:Tretinoin; D000097768:Retinoic Acid Receptor gamma; C508858:IL12A protein, human; C508585:IL1B protein, human; C508594:IL2 protein, human; C508840:IL23A protein, human; C000607071:RARA protein, human; C539900:RORC protein, human; C000607072:Rara protein, mouse