title: Complementarity and redundancy of IL-22-producing innate lymphoid cells.
abstract: Intestinal T cells and group 3 innate lymphoid cells (ILC3 cells) control the composition of the microbiota and gut immune responses. Within the gut, ILC3 subsets coexist that either express or lack the natural cytoxicity receptor (NCR) NKp46. We identified here the transcriptional signature associated with the transcription factor T-bet-dependent differentiation of NCR(-) ILC3 cells into NCR(+) ILC3 cells. Contrary to the prevailing view, we found by conditional deletion of the key ILC3 genes Stat3, Il22, Tbx21 and Mcl1 that NCR(+) ILC3 cells were redundant for the control of mouse colonic infection with Citrobacter rodentium in the presence of T cells. However, NCR(+) ILC3 cells were essential for cecal homeostasis. Our data show that interplay between intestinal ILC3 cells and adaptive lymphocytes results in robust complementary failsafe mechanisms that ensure gut homeostasis.
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, and Department of Medical Biology, University of Melbourne, Parkville, Australia.|Department of Medical Biology, University of Melbourne, Parkville, Australia.
authors.forename: Lucille C
authors.initials: LC
authors.lastname: Rankin
authors.affiliation: Centre d'Immunologie de Marseille-Luminy, Université d'Aix-Marseille UM2, Inserm, U1104, CNRS UMR7280, Marseille, France.
authors.forename: Mathilde J H
authors.initials: MJ
authors.lastname: Girard-Madoux
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, and Department of Medical Biology, University of Melbourne, Parkville, Australia.|Department of Medical Biology, University of Melbourne, Parkville, Australia.
authors.forename: Cyril
authors.initials: C
authors.lastname: Seillet
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, and Department of Medical Biology, University of Melbourne, Parkville, Australia.|Department of Medical Biology, University of Melbourne, Parkville, Australia.
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Mielke
authors.affiliation: Centre d'Immunologie de Marseille-Luminy, Université d'Aix-Marseille UM2, Inserm, U1104, CNRS UMR7280, Marseille, France.
authors.forename: Yann
authors.initials: Y
authors.lastname: Kerdiles
authors.affiliation: Centre d'Immunologie de Marseille-Luminy, Université d'Aix-Marseille UM2, Inserm, U1104, CNRS UMR7280, Marseille, France.
authors.forename: Aurore
authors.initials: A
authors.lastname: Fenis
authors.affiliation: Centre d'Immunologie de Marseille-Luminy, Université d'Aix-Marseille UM2, Inserm, U1104, CNRS UMR7280, Marseille, France.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Wieduwild
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, and Department of Medical Biology, University of Melbourne, Parkville, Australia.|Department of Medical Biology, University of Melbourne, Parkville, Australia.
authors.forename: Tracy
authors.initials: T
authors.lastname: Putoczki
authors.affiliation: Labex Milieu Intérieur, Institut Pasteur, Paris, France.
authors.forename: Stanislas
authors.initials: S
authors.lastname: Mondot
authors.affiliation: Laboratoire d'Immunologie and Inserm U932, Institut Curie, Paris, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Lantz
authors.affiliation: Inflammation Research Center, VIB, Ghent University, Ghent, Belgium.|Department of Biochemistry, Ghent University, Ghent, Belgium.
authors.forename: Dieter
authors.initials: D
authors.lastname: Demon
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, and Department of Medical Biology, University of Melbourne, Parkville, Australia.|Department of Medical Biology, University of Melbourne, Parkville, Australia.
authors.forename: Anthony T
authors.identifier: http://orcid.org/0000-0002-1102-8506
authors.initials: AT
authors.lastname: Papenfuss
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, and Department of Medical Biology, University of Melbourne, Parkville, Australia.|Department of Medical Biology, University of Melbourne, Parkville, Australia.|Department of Mathematics and Statistics, University of Melbourne, Parkville, Australia.
authors.forename: Gordon K
authors.identifier: http://orcid.org/0000-0001-9221-2892
authors.initials: GK
authors.lastname: Smyth
authors.affiliation: Inflammation Research Center, VIB, Ghent University, Ghent, Belgium.|Department of Biochemistry, Ghent University, Ghent, Belgium.
authors.forename: Mohamed
authors.identifier: http://orcid.org/0000-0002-4898-7663
authors.initials: M
authors.lastname: Lamkanfi
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, and Department of Medical Biology, University of Melbourne, Parkville, Australia.|Department of Medical Biology, University of Melbourne, Parkville, Australia.|Boehringer-Ingelheim RCV, Vienna, Austria.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Carotta
authors.affiliation: Ludwig Institute for Cancer Research and Experimental Medicine Unit, Catholic University of Louvain, Brussels, Belgium.
authors.forename: Jean-Christophe
authors.identifier: http://orcid.org/0000-0003-1736-2131
authors.initials: JC
authors.lastname: Renauld
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, and Department of Medical Biology, University of Melbourne, Parkville, Australia.|Department of Medical Biology, University of Melbourne, Parkville, Australia.|Department of Computing and Information Systems, University of Melbourne, Parkville, Australia.
authors.forename: Wei
authors.initials: W
authors.lastname: Shi
authors.affiliation: MI-mAbs consortium Aix-Marseille University, Centre d'Immunologie de Marseille-Luminy, Marseille, France.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Carpentier
authors.affiliation: Bioinnovation, SANOFI, Boston, Massachusetts, USA.
authors.forename: Tim
authors.initials: T
authors.lastname: Soos
authors.affiliation: Bioinnovation, SANOFI, Boston, Massachusetts, USA.
authors.forename: Christopher
authors.initials: C
authors.lastname: Arendt
authors.affiliation: Centre d'Immunologie de Marseille-Luminy, Université d'Aix-Marseille UM2, Inserm, U1104, CNRS UMR7280, Marseille, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Ugolini
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, and Department of Medical Biology, University of Melbourne, Parkville, Australia.|Department of Medical Biology, University of Melbourne, Parkville, Australia.
authors.forename: Nicholas D
authors.initials: ND
authors.lastname: Huntington
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, and Department of Medical Biology, University of Melbourne, Parkville, Australia.|Department of Medical Biology, University of Melbourne, Parkville, Australia.
authors.forename: Gabrielle T
authors.initials: GT
authors.lastname: Belz
authors.affiliation: Centre d'Immunologie de Marseille-Luminy, Université d'Aix-Marseille UM2, Inserm, U1104, CNRS UMR7280, Marseille, France.|Immunologie, Hôpital de la Conception, Assistance Publique-Hôpitaux de Marseille, Marseille, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Vivier
mesh_terms: D000818:Animals; D044082:Citrobacter rodentium / Q000276:immunology; D016000:Cluster Analysis; D004195:Disease Models, Animal; D004756:Enterobacteriaceae Infections / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006706:Homeostasis; D007113:Immunity, Innate; D007378:Interleukins / Q000096:biosynthesis*; D016131:Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D008214:Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D064549:Myeloid Cell Leukemia Sequence 1 Protein / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D055627:Natural Cytotoxicity Triggering Receptor 1 / Q000378:metabolism; D015398:Signal Transduction; D020825:T-Box Domain Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D059467:Transcriptome; D000097043:Interleukin-22; D000098815:T-bet Transcription Factor
chemical_list: D007378:Interleukins; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D055627:Natural Cytotoxicity Triggering Receptor 1; D020825:T-Box Domain Proteins; D000097043:Interleukin-22; D000098815:T-bet Transcription Factor