| First Author | Michel ML | Year | 2016 |
| Journal | Eur J Immunol | Volume | 46 |
| Issue | 9 | Pages | 2162-74 |
| PubMed ID | 27338553 | Mgi Jnum | J:246878 |
| Mgi Id | MGI:5924521 | Doi | 10.1002/eji.201646313 |
| Citation | Michel ML, et al. (2016) SLAM-associated protein favors the development of iNKT2 over iNKT17 cells. Eur J Immunol 46(9):2162-74 |
| abstractText | Invariant NKT (iNKT) cells differentiate in the thymus into three distinct lineages defined by their cytokine and transcription factor expression. Signaling lymphocyte activation molecule (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 Valpha14-Jalpha18 TCRalpha 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-gamma-producing iNKT1 differentiation is only moderately compromised. Lack of SAP reduced the expression of the transcription factors GATA-3 and promyelocytic leukemia zinc finger, but enhanced the levels of retinoic acid receptor-related orphan receptor gammat. In the absence of SAP, lineage commitment was actually shifted toward the emergence of iNKT17 over iNKT2 cells. Collectively, our data unveil a new critical regulatory function for SAP in thymic iNKT cell fate decisions. |
