Lien vers Pubmed [PMID] – 27338553
Eur. J. Immunol. 2016 Jun;
Invariant Natural Killer T (iNKT) cells differentiate in the thymus into three distinct lineages defined by their cytokine and transcription factor expression. SLAM-associated protein (SAP) is essential for early stages of iNKT cell development, but its role during terminal differentiation of iNKT1, iNKT2 or iNKT17 cells remains unclear. Taking advantage of SAP-deficient mice expressing a Vα14-Jα18 TCRα transgene, we found that SAP is critical not only for IL-4 production but also for the terminal differentiation of IL-4-producing iNKT2 cells. Furthermore, without SAP, the IL-17-producing subset is expanded, while IFN-γ producing iNKT1 differentiation is only moderately compromised. Lack of SAP reduced the expression of the transcription factors GATA-3 and PLZF, but enhanced the levels of RORγt. In the absence of SAP, lineage commitment was actually shifted towards the emergence of iNKT17 over iNKT2 cells. Collectively, our data unveil a new critical regulatory function for SAP in thymic iNKT cell fate decisions. This article is protected by copyright. All rights reserved.