title: Cutting edge: crucial role of IL-1 and IL-23 in the innate IL-17 response of peripheral lymph node NK1.1- invariant NKT cells to bacteria.
abstract: We have shown previously that peripheral lymph node-resident retinoic acid receptor-related orphan receptor γt(+) NK1.1(-) invariant NKT (iNKT) cells produce IL-17A independently of IL-6. In this study, we show that the concomitant presence of IL-1 and IL-23 is crucial to induce a rapid and sustained IL-17A/F and IL-22 response by these cells that requires TCR-CD1d interaction and partly relies on IL-23-mediated upregulation of IL-23R and IL-1R1 expression. We further show that IL-1 and IL-23 produced by pathogen-associated molecular pattern-stimulated dendritic cells induce this response from NK1.1(-) iNKT cells in vitro, involving mainly TLR2/4-signaling pathways. Finally, we found that IL-17A production by these cells occurs very early and transiently in vivo in response to heat-killed bacteria. Overall, our study indicates that peripheral lymph node NK1.1(-) iNKT cells could be a source of innate Th17-related cytokines during bacterial infections and supports the hypothesis that they are able to provide an efficient first line of defense against bacterial invasion.
authors.affiliation: INSERM U561, Hôpital Cochin St. Vincent de Paul, Université René-Descartes, 75014 Paris, France.
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Doisne
authors.forename: Valérie
authors.initials: V
authors.lastname: Soulard
authors.forename: Chantal
authors.initials: C
authors.lastname: Bécourt
authors.forename: Latiffa
authors.initials: L
authors.lastname: Amniai
authors.forename: Pauline
authors.initials: P
authors.lastname: Henrot
authors.forename: Colin
authors.initials: C
authors.lastname: Havenar-Daughton
authors.forename: Charlène
authors.initials: C
authors.lastname: Blanchet
authors.forename: Laurence
authors.initials: L
authors.lastname: Zitvogel
authors.forename: Bernhard
authors.initials: B
authors.lastname: Ryffel
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Cavaillon
authors.forename: Julien C
authors.initials: JC
authors.lastname: Marie
authors.forename: Isabelle
authors.initials: I
authors.lastname: Couillin
authors.forename: Kamel
authors.initials: K
authors.lastname: Benlagha
mesh_terms: D000818:Animals; D000950:Antigens, Ly / Q000096:biosynthesis*; D002478:Cells, Cultured; D020566:Dendritic Cells, Follicular / Q000276:immunology / Q000378:metabolism; D004926:Escherichia coli / Q000276:immunology*; D007113:Immunity, Innate / Q000235:genetics; D020381:Interleukin-17 / Q000096:biosynthesis*; D053583:Interleukin-1beta / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology*; D053759:Interleukin-23 / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology*; D007378:Interleukins / Q000096:biosynthesis; D008198:Lymph Nodes / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D055651:NK Cell Lectin-Like Receptor Subfamily B / Q000096:biosynthesis*; D055611:Natural Killer T-Cells / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D018168:Receptors, Retinoic Acid / Q000502:physiology; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology; D013211:Staphylococcus aureus / Q000276:immunology*; D000097043:Interleukin-22; D000097768:Retinoic Acid Receptor gamma
chemical_list: D000950:Antigens, Ly; D020381:Interleukin-17; D053583:Interleukin-1beta; D053759:Interleukin-23; D007378:Interleukins; D055651:NK Cell Lectin-Like Receptor Subfamily B; D018168:Receptors, Retinoic Acid; D000097043:Interleukin-22; D000097768:Retinoic Acid Receptor gamma; C527211:Klrb1c protein, mouse