Immunity
Volume 43, Issue 1, 21 July 2015, Pages 146-160
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Article
Interleukin-12 and -23 Control Plasticity of CD127+ Group 1 and Group 3 Innate Lymphoid Cells in the Intestinal Lamina Propria

https://doi.org/10.1016/j.immuni.2015.06.019Get rights and content
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Highlights

  • CD127+ ILC1 can differentiate into ILC3

  • Differentiation of ILC1 to ILC3 is reversible

  • Differentiation of ILC1 to ILC3 is driven by IL-23 and accelerated by IL-1β and RA

  • Distinct dendritic cell subsets induce differentiation of ILC1 to ILC3 and vice versa

Summary

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.

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