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Publication : SOX4 controls invariant NKT cell differentiation by tuning TCR signaling.

First Author  Malhotra N Year  2018
Journal  J Exp Med Volume  215
Issue  11 Pages  2887-2900
PubMed ID  30287480 Mgi Jnum  J:269365
Mgi Id  MGI:6273136 Doi  10.1084/jem.20172021
Citation  Malhotra N, et al. (2018) SOX4 controls invariant NKT cell differentiation by tuning TCR signaling. J Exp Med 215(11):2887-2900
abstractText  Natural killer T (NKT) cells expressing the invariant T cell receptor (iTCR) serve an essential function in clearance of certain pathogens and have been implicated in autoimmune and allergic diseases. Complex effector programs of these iNKT cells are wired in the thymus, and upon thymic egress, they can respond within hours of antigenic challenges, classifying iNKT cells as innate-like. It has been assumed that the successful rearrangement of the invariant iTCRalpha chain is the central event in the divergence of immature thymocytes to the NKT cell lineage, but molecular properties that render the iTCR signaling distinct to permit the T cell lineage diversification remain obscure. Here we show that the High Mobility Group (HMG) transcription factor (TF) SOX4 controls the production of iNKT cells by inducing MicroRNA-181 (Mir181) to enhance TCR signaling and Ca(2+) fluxes in precursors. These results suggest the existence of tailored, permissive gene circuits in iNKT precursors for innate-like T cell development.
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