| First Author | Zhang X | Year | 2020 |
| Journal | Cell Mol Immunol | Volume | 17 |
| Issue | 4 | Pages | 395-406 |
| PubMed ID | 31076725 | Mgi Jnum | J:308375 |
| Mgi Id | MGI:6718224 | Doi | 10.1038/s41423-019-0234-0 |
| Citation | Zhang X, et al. (2020) TRAF3IP3 at the trans-Golgi network regulates NKT2 maturation via the MEK/ERK signaling pathway. Cell Mol Immunol 17(4):395-406 |
| abstractText | Thymic natural killer T (NKT)2 cells are a subset of invariant NKT cells with PLZF(hi)GATA3(hi)IL-4(+). The differentiation of NKT2 cells is not fully understood. In the present study, we report an important role of TRAF3-interacting protein 3 (TRAF3IP3) in the functional maturation and expansion of committed NKT2s in thymic medulla. Mice with T-cell-specific deletion of TRAF3IP3 had decreased thymic NKT2 cells, decreased IL-4-producing peripheral iNKTs, and defects in response to alpha-galactosylceramide. Positive selection and high PLZF expression in CD24(+)CD44(-) and CCR7(+)CD44(-) immature iNKTs were not affected. Only CD44(hi)NK1.1(-) iNKTs in Traf3ip3(-/-) mice showed reduced expression of Egr2, PLZF, and IL-17RB, decreased proliferation, and reduced IL-4 production upon stimulation. This Egr2 and IL-4 expression was augmented by MEK1/ERK activation in iNKTs, and TRAF3IP3 at the trans-Golgi network recruited MEK1 and facilitated ERK phosphorylation and nuclear translocation. LTbetaR-regulated bone marrow-derived nonlymphoid cells in the medullary thymic microenvironment were required for MEK/ERK activation and NKT2 maturation. These data demonstrate an important functional maturation process in NKT2 differentiation that is regulated by MEK/ERK signaling at the trans-Golgi network. |
