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
N1 - Funding Information:
We are especially indebted to NIH Tetramer facilities for providing CD1d-PBS57 tetramers and grateful to Elke Schneider for discussions. We thank Professor Chi-Huey Wong for providing GSLGal. S.L. and M.L.D.M. are senior scientists of the Centre National de la Recherche Scientifique (France). This work was supported by grants from INSERM (Institut National de la Sant? et de la Recherche M?dicale), CNRS (Centre National de la Recherche Scientifique), ANR (Agence Nationale de la Recherche; ANR-08-MIEN-012-01, ANR-2010-MIDI-005, and ANR-10-IAHU-01), the Fondation ARC pour la Recherche sur le Cancer (France), the European Research Council (ERC-2009-AdG_20090506 n?FP7-249816), and the Rare Diseases Fondation (France). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
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
C2 - 27338553
AN - SCOPUS:84986005272
VL - 46
SP - 2162
EP - 2174
JO - European Journal of Immunology
JF - European Journal of Immunology
SN - 0014-2980
IS - 9
ER -