First Author | Vallabhapurapu S | Year | 2008 |
Journal | Eur J Immunol | Volume | 38 |
Issue | 12 | Pages | 3508-19 |
PubMed ID | 19003818 | Mgi Jnum | J:141395 |
Mgi Id | MGI:3818209 | Doi | 10.1002/eji.200737830 |
Citation | Vallabhapurapu S, et al. (2008) Rel/NF-kappaB family member RelA regulates NK1.1(-) to NK1.1(+) transition as well as IL-15-induced expansion of NKT cells. Eur J Immunol 38(12):3508-3519 |
abstractText | Development of NKT cells was shown to depend on lymphotoxin (LT) and IL-15 signaling pathways as well as on cytokine receptor common gamma 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-kappaB 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 alpha and gamma chains' expression in an NF-kappaB-dependent manner, suggesting a molecular mechanism by which NF-kappaB regulates NKT-cell development. NF-kappaB also regulates TCR-induced expression of LT-alpha and LT-beta 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. |