Rel/NF-kappa B family member RelA regulates NK1.1(-) to NK1.1(+) transition as well as IL-15-induced expansion of NKT cells

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 CD44hiNK1.1- 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. © 2008 Wiley-VCH Verlag GmbH & Co. KGaA.