Interleukin-12 and -23 Control Plasticity of CD127(+) Group 1 and Group 3 Innate Lymphoid Cells in the Intestinal Lamina Propria

Jochem H Bernink; Lisette Krabbendam; Kristine Germar; Esther de Jong; Konrad Gronke; Michael Kofoed-Nielsen; J Marius Munneke; Mette D Hazenberg; Julien Villaudy; Christianne J Buskens; Willem A Bemelman; Andreas Diefenbach; Bianca Blom; Hergen Spits

doi:10.1016/j.immuni.2015.06.019

Interleukin-12 and -23 Control Plasticity of CD127(+) Group 1 and Group 3 Innate Lymphoid Cells in the Intestinal Lamina Propria

Immunity. 2015 Jul 21;43(1):146-60. doi: 10.1016/j.immuni.2015.06.019. Epub 2015 Jul 14.

Affiliations

¹ Department of Cell Biology and Histology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands.
² Research Center Immunology and Institute of Medical Microbiology and Hygiene, University of Mainz Medical Centre, Obere Zahlbacher Strasse 67 D-55131 Mainz, Germany.
³ Department of Hematology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands.
⁴ Department of Medical Microbiology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands.
⁵ Department of Surgery, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands.
⁶ 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.

PMID: 26187413
DOI: 10.1016/j.immuni.2015.06.019

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.

Publication types

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

MeSH terms

Animals
Cell Differentiation / immunology
Cells, Cultured
Crohn Disease / immunology
Dendritic Cells / immunology
Humans
Interleukin-12 Subunit p35 / immunology*
Interleukin-1beta / immunology
Interleukin-2 / immunology
Interleukin-23 Subunit p19 / immunology*
Interleukin-7 Receptor alpha Subunit / immunology*
Intestinal Mucosa / cytology
Intestinal Mucosa / immunology*
Killer Cells, Natural / immunology
Lipopolysaccharide Receptors / immunology
Lymphocyte Transfusion
Lymphocytes / immunology*
Mice
Mice, Inbred C57BL
Mice, Inbred NOD
Mice, Knockout
Mice, SCID
Nuclear Receptor Subfamily 1, Group F, Member 3 / immunology
Receptors, Retinoic Acid / metabolism
Retinoic Acid Receptor alpha
Retinoic Acid Receptor gamma
Retinoid X Receptor gamma / metabolism
Tretinoin / pharmacology

Substances

IL12A protein, human
IL1B protein, human
IL2 protein, human
IL23A protein, human
Interleukin-12 Subunit p35
Interleukin-1beta
Interleukin-2
Interleukin-23 Subunit p19
Interleukin-7 Receptor alpha Subunit
Lipopolysaccharide Receptors
Nuclear Receptor Subfamily 1, Group F, Member 3
RARA protein, human
RORC protein, human
Rara protein, mouse
Receptors, Retinoic Acid
Retinoic Acid Receptor alpha
Retinoid X Receptor gamma
Tretinoin