| First Author | Bank U | Year | 2020 |
| Journal | Nat Commun | Volume | 11 |
| Issue | 1 | Pages | 1056 |
| PubMed ID | 32103006 | Mgi Jnum | J:287252 |
| Mgi Id | MGI:6401681 | Doi | 10.1038/s41467-020-14782-3 |
| Citation | Bank U, et al. (2020) c-FLIP is crucial for IL-7/IL-15-dependent NKp46(+) ILC development and protection from intestinal inflammation in mice. Nat Commun 11(1):1056 |
| abstractText | 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 of c-FLIP leads to the loss of all IL-7/IL-15-dependent NKp46(+) ILC, thereby inducing early-onset chronic colitis and subsequently microbial dysbiosis; meanwhile, the depletion of cNK, but not NKp46(+) ILC1/3, aggravates experimental colitis. In summary, our data demonstrate a non-redundant function of c-FLIP for the generation of NKp46(+) ILC, which protect T/B lymphocyte-sufficient mice from intestinal inflammation. |
