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 journalArticle

12 Citations (Scopus)

Abstract

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
Volume46
Issue number9
DOIs
Publication statusPublished - Sep 1 2016

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Lymphocyte Activation
Natural Killer T-Cells
Proteins
Interleukin-4
Transcription Factor 3
Retinoic Acid Receptors
Interleukin-17
Zinc Fingers
Transgenes
Thymus Gland
Leukemia
Transcription Factors
Signaling Lymphocytic Activation Molecule Associated Protein
Cytokines

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Cite this

Michel, M. L., Lenoir, C., Massot, B., Diem, S., Pasquier, B., Sawa, S., ... Latour, S. (2016). SLAM-associated protein favors the development of iNKT2 over iNKT17 cells. European Journal of Immunology, 46(9), 2162-2174. https://doi.org/10.1002/eji.201646313

SLAM-associated protein favors the development of iNKT2 over iNKT17 cells. / Michel, Marie Laure; Lenoir, Christelle; Massot, Bérangère; Diem, Séverine; Pasquier, Benoit; Sawa, Shinichiro; Rignault-Bricard, Rachel; Lehuen, Agnès; Eberl, Gérard; Veillette, André; Leite-de-Moraes, Maria; Latour, Sylvain.

In: European Journal of Immunology, Vol. 46, No. 9, 01.09.2016, p. 2162-2174.

Research output: Contribution to journalArticle

Michel, ML, Lenoir, C, Massot, B, Diem, S, Pasquier, B, Sawa, S, Rignault-Bricard, R, Lehuen, A, Eberl, G, Veillette, A, Leite-de-Moraes, M & Latour, S 2016, 'SLAM-associated protein favors the development of iNKT2 over iNKT17 cells', European Journal of Immunology, vol. 46, no. 9, pp. 2162-2174. https://doi.org/10.1002/eji.201646313
Michel, Marie Laure ; Lenoir, Christelle ; Massot, Bérangère ; Diem, Séverine ; Pasquier, Benoit ; Sawa, Shinichiro ; Rignault-Bricard, Rachel ; Lehuen, Agnès ; Eberl, Gérard ; Veillette, André ; Leite-de-Moraes, Maria ; Latour, Sylvain. / SLAM-associated protein favors the development of iNKT2 over iNKT17 cells. In: European Journal of Immunology. 2016 ; Vol. 46, No. 9. pp. 2162-2174.
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