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

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491 Citations (Scopus)

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
Original languageEnglish
Pages (from-to)146-160
JournalImmunity
Volume43
Issue number1
DOIs
Publication statusPublished - 2015

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