C-FLIP is crucial for IL-7/IL-15-dependent NKp46⁺ ILC development and protection from intestinal inflammation in mice.

ABSTRACT: NKp46⁺ innate lymphoid cells (ILC) modulate tissue homeostasis and anti-microbial immune responses. ILC development and function are regulated by cytokines such as Interleukin (IL)-7 and IL-15. However, the ILC-intrinsic pathways translating cytokine signals into developmental programs are largely unknown. Here we show that the anti-apoptotic molecule cellular FLICE-like inhibitory protein (c-FLIP) is crucial for the generation of IL-7/IL-15-dependent NKp46⁺ ILC1, including conventional natural killer (cNK) cells, and ILC3. Cytokine-induced phosphorylation of signal transducer and activator of transcription 5 (STAT5) precedes up-regulation of c-FLIP, which protects developing NKp46⁺ ILC from TNF-induced apoptosis. NKp46⁺ ILC-specific inactivation

SUBMITTER: Bank U 

PROVIDER: S-EPMC7044440 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature