التفاصيل البيبلوغرافية
| العنوان: |
Nur77 controls tolerance induction, terminal differentiation, and effector functions in semi-invariant natural killer T cells. |
| المؤلفون: |
Kumar, Amrendra, Hill, Timothy M., Gordy, Laura E., Suryadevara, Naveenchandra, Lan Wu, Flyak, Andrew I., Bezbradica, Jelena S., Luc Van Kaer, Joyce, Sebastian |
| المصدر: |
Proceedings of the National Academy of Sciences of the United States of America; 7/21/2020, Vol. 117 Issue 29, p17156-17165, 10p |
| مصطلحات موضوعية: |
CYTOTOXIC T cells, KILLER cells, BONE marrow cells, T cell receptors, THYMOCYTES |
| مستخلص: |
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 (Nur77tg) in mouse thymocytes abrogates iNKT cell development. Introgression of a rearranged Va14-Ja18 TCR-a chain gene into the Nur77tg (Nur77tg;Va14tg) 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- γ-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. [ABSTRACT FROM AUTHOR] |
|
Copyright of Proceedings of the National Academy of Sciences of the United States of America is the property of National Academy of Sciences and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) |
| قاعدة البيانات: |
Complementary Index |
Full Text Finder