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Immunity. 2018 Jun 19;48(6):1208-1219.e4. doi: 10.1016/j.immuni.2018.04.012. Epub 2018 May 29.

The Tumor Necrosis Factor Superfamily Member RANKL Suppresses Effector Cytokine Production in Group 3 Innate Lymphoid Cells.

Author information

1
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, 63110, USA.
2
Institute for Oral Science, Matsumoto Dental University, 1780 Hirooka Gohara, Shiojiri Nagano, 399-0781, Japan.
3
Department of Immunology, University of Toronto, Sunnybrook Research Institute, Toronto, ON, M4N 3M5, Canada.
4
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, 63110, USA. Electronic address: mcolonna@wustl.edu.

Abstract

While signals that activate group 3 innate lymphoid cells (ILC3s) have been described, the factors that negatively regulate these cells are less well understood. Here we found that the tumor necrosis factor (TNF) superfamily member receptor activator of nuclear factor κB ligand (RANKL) suppressed ILC3 activity in the intestine. Deletion of RANKL in ILC3s and T cells increased C-C motif chemokine receptor 6 (CCR6)+ ILC3 abundance and enhanced production of interleukin-17A (IL-17A) and IL-22 in response to IL-23 and during infection with the enteric murine pathogen Citrobacter rodentium. Additionally, CCR6+ ILC3s produced higher amounts of the master transcriptional regulator RORγt at steady state in the absence of RANKL. RANKL-mediated suppression was independent of T cells, and instead occurred via interactions between CCR6+ ILC3s that expressed both RANKL and its receptor, RANK. Thus, RANK-RANKL interactions between ILC3s regulate ILC3 abundance and activation, suggesting that cell clustering may control ILC3 activity.

PMID:
29858011
PMCID:
PMC6086389
[Available on 2019-06-19]
DOI:
10.1016/j.immuni.2018.04.012

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