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

journal contribution
posted on 2023-05-17, 07:48 authored by Vallabhapurapu, S, Powolny-Budnicka, I, Riemann, M, Schmid, RM, Paxian, S, Pfeffer, K, Heinrich KornerHeinrich Korner, Weih, Falk
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.


Publication title

European Journal of Immunology










Menzies Institute for Medical Research


Wiley-V C H Verlag Gmbh

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Po Box 10 11 61, Weinheim, Germany, D-69451

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