SLAM-associated protein favors the development of iNKT2 over iNKT17 cells

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• 作者：Marie-Laure Michel ; Christelle Lenoir ; Bé ; rangè ; re Massot ; Sé ; verine Diem ; Benoit Pasquier ; Shinichiro Sawa ; Rachel Rignault-Bricard ; Agnè ; s Lehuen ; Gé ; rard Eberl ; André ; Veillette ; Maria Leite-de-Moraes and Sylvain Latour
• 刊名：European Journal of Immunology
• 出版年：2016
• 出版时间：September 2016
• 年：2016
• 卷：46
• 期：9
• 页码：2162-2174
• 全文大小：1631K
• ISSN：1521-4141

文摘

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 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 promyelocytic leukemia zinc finger, but enhanced the levels of retinoic acid receptor-related orphan receptor γt. 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.