| First Author | Ohara D | Year | 2024 |
| Journal | J Exp Med | Volume | 221 |
| Issue | 2 | PubMed ID | 38180443 |
| Mgi Jnum | J:345939 | Mgi Id | MGI:7595985 |
| Doi | 10.1084/jem.20230923 | Citation | Ohara D, et al. (2024) Notch2 with retinoic acid license IL-23 expression by intestinal EpCAM+ DCIR2+ cDC2s in mice. J Exp Med 221(2) |
| abstractText | Despite the importance of IL-23 in mucosal host defense and disease pathogenesis, the mechanisms regulating the development of IL-23-producing mononuclear phagocytes remain poorly understood. Here, we employed an Il23aVenus reporter strain to investigate the developmental identity and functional regulation of IL-23-producing cells. We showed that flagellin stimulation or Citrobacter rodentium infection led to robust induction of IL-23-producing EpCAM+ DCIR2+ CD103- cDC2s, termed cDCIL23, which was confined to gut-associated lymphoid tissues, including the mesenteric lymph nodes, cryptopatches, and isolated lymphoid follicles. Furthermore, we demonstrated that Notch2 signaling was crucial for the development of EpCAM+ DCIR2+ cDC2s, and the combination of Notch2 signaling with retinoic acid signaling controlled their terminal differentiation into cDCIL23, supporting a two-step model for the development of gut cDCIL23. Our findings provide fundamental insights into the developmental pathways and cellular dynamics of IL-23-producing cDC2s at steady state and during pathogen infection. |
