Temporal regulation of Wnt/ß-catenin signaling is important for invariant NKT cell development and terminal maturation.
Mol Immunol
; 85: 47-56, 2017 05.
Article
em En
| MEDLINE
| ID: mdl-28208073
ABSTRACT
The Wnt/ß-catenin signaling pathway plays important roles during various cellular functions including survival and proliferation of immune cells. The critical role of this pathway in conventional T cell development is established but little is known about its contributions to innate T cell development. In this study, we found that ß-catenin level, an indication of the strength of Wnt/ß-catenin signaling, is regulated during invariant NKT (iNKT) cell development. ß-catenin levels were greatly increased during iNKT cell selection from double positive thymocytes to Stage 0 of iNKT cell development and during subsequent development to Stage 1. Thereafter, ß-catenin levels decrease from Stage 2, which is essential for the terminal maturation of iNKT cells. Failure to dampen Wnt/ß-catenin signaling as in mice expressing a stabilized active form of ß-catenin (CATtg) resulted in increased Stage 2 and decreased Stage 3 iNKT cells. Inefficient transition from Stage 2 to 3 in CATtg iNKT cells seems to be contributed by poor expression of IL-15R (CD122) and transcription factor T-bet, both of which are necessary for terminal maturation of iNKT cells in the thymus. Consequently, IFN-γ+ iNKT cells were greatly reduced in CATtg mice. Together, our findings reveal that proper regulation of ß-catenin and in turn Wnt signaling plays an important role in the terminal maturation and function of iNKT cells.
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Base de dados:
MEDLINE
Assunto principal:
Diferenciação Celular
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Células T Matadoras Naturais
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Via de Sinalização Wnt
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article