| First Author | Mikami Y | Year | 2018 |
| Journal | Eur J Immunol | Volume | 48 |
| Issue | 7 | Pages | 1174-1180 |
| PubMed ID | 29524223 | Mgi Jnum | J:265084 |
| Mgi Id | MGI:6188656 | Doi | 10.1002/eji.201847480 |
| Citation | Mikami Y, et al. (2018) NCR(+) ILC3 maintain larger STAT4 reservoir via T-BET to regulate type 1 features upon IL-23 stimulation in mice. Eur J Immunol 48(7):1174-1180 |
| abstractText | Innate lymphoid cells (ILCs) producing IL-22 and/or IL-17, designated as ILC3, comprise a heterogeneous subset of cells involved in regulation of gut barrier homeostasis and inflammation. Exogenous environmental cues in conjunction with regulated expression of endogenous factors are key determinants of plasticity of ILC3 toward the type 1 fate. Herein, by using mouse models and transcriptomic approaches, we defined at the molecular level, initial events driving ILC3 expressing natural cytotoxicity receptors (NCR(+) ILC3) to acquire type 1 features. We observed that NCR(+) ILC3 exhibited high basal expression of the signal-dependent transcription factor STAT4 due to T-BET, leading to predisposed potential for the type 1 response. We found that the prototypical inducer of type 3 response, IL-23, played a predominant role over IL-12 by accessing STAT4 and preferentially inducing its phosphorylation in ILC3 expressing T-BET. The early effector program driven by IL-23 was characterized by the expression of IL-22, followed by a production of IFN-gamma, which relies on STAT4, T-BET and required chromatin remodeling of the Ifng locus. Altogether, our findings shed light on a feed-forward mechanism involving STAT4 and T-BET that modulates the outcome of IL-23 signaling in ILC3. |
