Complementarity and redundancy of IL-22-producing innate lymphoid cells

Lucille C Rankin; Mathilde J H Girard-Madoux; Cyril Seillet; Lisa A Mielke; Yann Kerdiles; Aurore Fenis; Elisabeth Wieduwild; Tracy Putoczki; Stanislas Mondot; Olivier Lantz; Dieter Demon; Anthony T Papenfuss; Gordon K Smyth; Mohamed Lamkanfi; Sebastian Carotta; Jean-Christophe Renauld; Wei Shi; Sabrina Carpentier; Tim Soos; Christopher Arendt; Sophie Ugolini; Nicholas D Huntington; Gabrielle T Belz; Eric Vivier

doi:10.1038/ni.3332

Complementarity and redundancy of IL-22-producing innate lymphoid cells

Nat Immunol. 2016 Feb;17(2):179-86. doi: 10.1038/ni.3332. Epub 2015 Nov 30.

Authors

Lucille C Rankin^{1

2}, Mathilde J H Girard-Madoux³, Cyril Seillet^{1

2}, Lisa A Mielke^{1

2}, Yann Kerdiles³, Aurore Fenis³, Elisabeth Wieduwild³, Tracy Putoczki^{1

2}, Stanislas Mondot⁴, Olivier Lantz⁵, Dieter Demon^{6

7}, Anthony T Papenfuss^{1

2}, Gordon K Smyth^{1

2

8}, Mohamed Lamkanfi^{6

7}, Sebastian Carotta^{1

2

9}, Jean-Christophe Renauld¹⁰, Wei Shi^{1

2

11}, Sabrina Carpentier¹², Tim Soos¹³, Christopher Arendt¹³, Sophie Ugolini³, Nicholas D Huntington^{1

2}, Gabrielle T Belz^{1

2}, Eric Vivier^{3

14}

Affiliations

¹ The Walter and Eliza Hall Institute of Medical Research, and Department of Medical Biology, University of Melbourne, Parkville, Australia.
² Department of Medical Biology, University of Melbourne, Parkville, Australia.
³ Centre d'Immunologie de Marseille-Luminy, Université d'Aix-Marseille UM2, Inserm, U1104, CNRS UMR7280, Marseille, France.
⁴ Labex Milieu Intérieur, Institut Pasteur, Paris, France.
⁵ Laboratoire d'Immunologie and Inserm U932, Institut Curie, Paris, France.
⁶ Inflammation Research Center, VIB, Ghent University, Ghent, Belgium.
⁷ Department of Biochemistry, Ghent University, Ghent, Belgium.
⁸ Department of Mathematics and Statistics, University of Melbourne, Parkville, Australia.
⁹ Boehringer-Ingelheim RCV, Vienna, Austria.
¹⁰ Ludwig Institute for Cancer Research and Experimental Medicine Unit, Catholic University of Louvain, Brussels, Belgium.
¹¹ Department of Computing and Information Systems, University of Melbourne, Parkville, Australia.
¹² MI-mAbs consortium Aix-Marseille University, Centre d'Immunologie de Marseille-Luminy, Marseille, France.
¹³ Bioinnovation, SANOFI, Boston, Massachusetts, USA.
¹⁴ Immunologie, Hôpital de la Conception, Assistance Publique-Hôpitaux de Marseille, Marseille, France.

PMID: 26595889
PMCID: PMC4720992
DOI: 10.1038/ni.3332

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Citrobacter rodentium / immunology
Cluster Analysis
Disease Models, Animal
Enterobacteriaceae Infections / genetics
Enterobacteriaceae Infections / immunology
Enterobacteriaceae Infections / metabolism
Enterobacteriaceae Infections / mortality
Enterobacteriaceae Infections / pathology
Female
Gene Expression Profiling
Gene Expression Regulation
Homeostasis
Immunity, Innate*
Interleukin-22
Interleukins / biosynthesis*
Lymphocyte Subsets / immunology
Lymphocyte Subsets / metabolism
Lymphocytes / immunology*
Lymphocytes / metabolism*
Male
Mice
Mice, Knockout
Mice, Transgenic
Myeloid Cell Leukemia Sequence 1 Protein / deficiency
Myeloid Cell Leukemia Sequence 1 Protein / genetics
Myeloid Cell Leukemia Sequence 1 Protein / metabolism
Natural Cytotoxicity Triggering Receptor 1 / metabolism
Signal Transduction
T-Box Domain Proteins / deficiency
T-Box Domain Proteins / genetics
T-Box Domain Proteins / metabolism
Transcriptome

Substances

Interleukins
Myeloid Cell Leukemia Sequence 1 Protein
Natural Cytotoxicity Triggering Receptor 1
T-Box Domain Proteins
T-box transcription factor TBX21

Grants and funding

268537/ERC_/European Research Council/International