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

Marie Laure Michel, Christelle Lenoir, Bérangère Massot, Séverine Diem, Benoit Pasquier, Shinichiro Sawa, Rachel Rignault-Bricard, Agnès Lehuen, Gérard Eberl, André Veillette, Maria Leite-de-Moraes, Sylvain Latour

Research output: Contribution to journalArticlepeer-review

18 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)2162-2174
Number of pages13
JournalEuropean Journal of Immunology
Issue number9
Publication statusPublished - Sept 1 2016
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology


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