Phenotypic and Functional Plasticity of Murine Intestinal NKp46+ Group 3 Innate Lymphoid Cells
Open Access
- 1 June 2016
- journal article
- research article
- Published by Oxford University Press (OUP) in The Journal of Immunology
- Vol. 196 (11) , 4731-4738
Abstract
Group 3 innate lymphoid cells (ILC3) actively participate in mucosal defense and homeostasis through prompt secretion of IL-17A, IL-22, and IFN-γ. Reports identify two ILC3 lineages: a CCR6+T-bet− subset that appears early in embryonic development and promotes lymphoid organogenesis and a CCR6−T-bet+ subset that emerges after microbial colonization and harbors NKp46+ ILC3. We demonstrate that NKp46 expression in the ILC3 subset is highly unstable. Cell fate mapping using Ncr1CreGFP × Rosa26RFP mice revealed the existence of an intestinal RFP+ ILC3 subset (Ncr1FM) lacking NKp46 expression at the transcript and protein levels. Ncr1FM ILC3 produced more IL-22 and were distinguishable from NKp46+ ILC3 by differential CD117, CD49a, DNAX accessory molecule-1, and, surprisingly, CCR6 expression. Ncr1FM ILC3 emerged after birth and persisted in adult mice following broad-spectrum antibiotic treatment. These results identify an unexpected phenotypic instability within NKp46+ ILC3 that suggests a major role for environmental signals in tuning ILC3 functional plasticity.Keywords
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