Phenotypic and Functional Plasticity of Murine Intestinal NKp46+ Group 3 Innate Lymphoid Cells

Thomas Verrier (1, 2) , Naoko Satoh-Takayama (3, 1) , Nicolas Serafini (1) , Solenne Marie (1) , James P Di Santo (1) , Christian A. J. Vosshenrich (1)

1 Immunité Innée - Innate Immunity
2 UPD7 - Université Paris Diderot - Paris 7
3 RIKEN IMS - Laboratory for Intestinal Ecosystem [Yokohama]

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.

Domaines: Immunité innée

Thomas Verrier, Naoko Satoh-Takayama, Nicolas Serafini, Solenne Marie, James P Di Santo, et al.. Phenotypic and Functional Plasticity of Murine Intestinal NKp46+ Group 3 Innate Lymphoid Cells. Journal of Immunology, 2016, 196 (11), pp.4731-4738. ⟨10.4049/jimmunol.1502673⟩. ⟨hal-01370691⟩