Rel/NF-κB family member RelA regulates NK1.1− to NK1.1+ transition as well as IL-15-induced expansion of NKT cells
✍ Scribed by Sivakumar Vallabhapurapu; Iwona Powolny-Budnicka; Marc Riemann; Roland M. Schmid; Stephan Paxian; Klaus Pfeffer; Heinrich Körner; Falk Weih
- Book ID
- 102168479
- Publisher
- John Wiley and Sons
- Year
- 2008
- Tongue
- English
- Weight
- 436 KB
- Volume
- 38
- Category
- Article
- ISSN
- 0014-2980
No coin nor oath required. For personal study only.
✦ Synopsis
Abstract
Development of NKT cells was shown to depend on lymphotoxin (LT) and IL‐15 signaling pathways as well as on cytokine receptor common γ chain. After positive selection, NKT‐cell precursors transit through progressive maturation stages including proliferative expansion within the NK1.1^−^ window. The transcription factors that integrate different signaling pathways into different stages of NKT‐cell development are not well characterized. Here, we show that the Rel/NF‐κB family member RelA regulates the NK1.1^−^ to NK1.1^+^ transition during NKT‐cell development. RelA is also required for both IL‐15‐ and IL‐7‐induced proliferation of CD44^hi^NK1.1^−^ NKT‐cell precursors. Activation of the invariant NKT‐cell receptor induces both IL‐15 receptor α and γ chains' expression in an NF‐κB‐dependent manner, suggesting a molecular mechanism by which NF‐κB regulates NKT‐cell development. NF‐κB also regulates TCR‐induced expression of LT‐α and LT‐β within NKT cells. In contrast to previous reports, however, we show that LT signaling is dispensable for thymic NKT‐cell development but is essential for their colonization of peripheral organs such as liver.