| First Author | Kumar A | Year | 2020 |
| Journal | Proc Natl Acad Sci U S A | Volume | 117 |
| Issue | 29 | Pages | 17156-17165 |
| PubMed ID | 32611812 | Mgi Jnum | J:292183 |
| Mgi Id | MGI:6447529 | Doi | 10.1073/pnas.2001665117 |
| Citation | Kumar A, et al. (2020) Nur77 controls tolerance induction, terminal differentiation, and effector functions in semi-invariant natural killer T cells. Proc Natl Acad Sci U S A 117(29):17156-17165 |
| abstractText | Semi-invariant natural killer T (iNKT) cells are self-reactive lymphocytes, yet how this lineage attains self-tolerance remains unknown. iNKT cells constitutively express high levels of Nr4a1-encoded Nur77, a transcription factor that integrates signal strength downstream of the T cell receptor (TCR) within activated thymocytes and peripheral T cells. The function of Nur77 in iNKT cells is unknown. Here we report that sustained Nur77 overexpression (Nur77(tg)) in mouse thymocytes abrogates iNKT cell development. Introgression of a rearranged Valpha14-Jalpha18 TCR-alpha chain gene into the Nur77(tg) (Nur77(tg);Valpha14(tg)) mouse rescued iNKT cell development up to the early precursor stage, stage 0. iNKT cells in bone marrow chimeras that reconstituted thymic cellularity developed beyond stage 0 precursors and yielded IL-4-producing NKT2 cell subset but not IFN-gamma-producing NKT1 cell subset. Nonetheless, the developing thymic iNKT cells that emerged in these chimeras expressed the exhaustion marker PD1 and responded poorly to a strong glycolipid agonist. Thus, Nur77 integrates signals emanating from the TCR to control thymic iNKT cell tolerance induction, terminal differentiation, and effector functions. |
