[PDF][PDF] Interleukin-12 and-23 control plasticity of CD127+ group 1 and group 3 innate lymphoid cells in the intestinal lamina propria

JH Bernink, L Krabbendam, K Germar, E de Jong… - Immunity, 2015 - cell.com
JH Bernink, L Krabbendam, K Germar, E de Jong, K Gronke, M Kofoed-Nielsen…
Immunity, 2015cell.com
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 …
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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