ReI/NF-kB family member ReIA regulates NK1.1- to NK1.1+ transition as well as IL-15-induced expansion of NKT cells

Abstract

Development of NKT cells was shown to depend on lymphotoxin (LT) and IL-15 signaling pathways as well as on cytokine receptor common 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 ReI/NF-B family member ReIA regulates the NK1.1- to NK1.1+ transition during NKT-cell development. ReIA 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 and chains' expression in an NF-B-dependent manner, suggesting a molecular mechanism by which NF-B regulates NKT-cell development. NF-B also regulates TCR-induced expression of LT- and LT- 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.