Phenotypic and Functional Plasticity of Murine Intestinal NKp46+ Group 3 Innate Lymphoid Cells.
Thomas VerrierNaoko Satoh-TakayamaNicolas SerafiniSolenne MarieJames P Di SantoChristian A J VosshenrichPublished in: Journal of immunology (Baltimore, Md. : 1950) (2016)
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 Ncr1(CreGFP) × Rosa26(RFP) mice revealed the existence of an intestinal RFP(+) ILC3 subset (Ncr1(FM)) lacking NKp46 expression at the transcript and protein levels. Ncr1(FM) ILC3 produced more IL-22 and were distinguishable from NKp46(+) ILC3 by differential CD117, CD49a, DNAX accessory molecule-1, and, surprisingly, CCR6 expression. Ncr1(FM) 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.
Keyphrases
- nk cells
- poor prognosis
- induced apoptosis
- dendritic cells
- emergency department
- regulatory t cells
- type diabetes
- immune response
- high resolution
- adipose tissue
- signaling pathway
- small molecule
- high fat diet induced
- pregnant women
- cell proliferation
- endoplasmic reticulum stress
- risk assessment
- adverse drug
- single cell
- gestational age
- smoking cessation
- amino acid