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 language | English |
|---|---|
| Pages (from-to) | 2162-2174 |
| Number of pages | 13 |
| Journal | European Journal of Immunology |
| Volume | 46 |
| Issue number | 9 |
| DOIs | |
| Publication status | Published - Sep 1 2016 |
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All Science Journal Classification (ASJC) codes
- Immunology and Allergy
- Immunology
Cite this
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 journal › Article
}
TY - JOUR
T1 - SLAM-associated protein favors the development of iNKT2 over iNKT17 cells
AU - Michel, Marie Laure
AU - Lenoir, Christelle
AU - Massot, Bérangère
AU - Diem, Séverine
AU - Pasquier, Benoit
AU - Sawa, Shinichiro
AU - Rignault-Bricard, Rachel
AU - Lehuen, Agnès
AU - Eberl, Gérard
AU - Veillette, André
AU - Leite-de-Moraes, Maria
AU - Latour, Sylvain
PY - 2016/9/1
Y1 - 2016/9/1
N2 - 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.
AB - 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.
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U2 - 10.1002/eji.201646313
DO - 10.1002/eji.201646313
M3 - Article
VL - 46
SP - 2162
EP - 2174
JO - European Journal of Immunology
JF - European Journal of Immunology
SN - 0014-2980
IS - 9
ER -