Rel/NF-kappa B family member RelA regulates NK1.1(-) to NK1.1(+) transition as well as IL-15-induced expansion of NKT cells
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posted on 2024-09-17, 02:08 authored by S Vallabhapurapu, I Powolny-Budnicka, M Riemann, RM Schmid, S Paxian, K Pfeffer, Heinrich KornerHeinrich Korner, Falk WeihDevelopment 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.
History
Publication title
European Journal of ImmunologyVolume
38Issue
12Pagination
3508-3519ISSN
0014-2980Department/School
Menzies Institute for Medical ResearchPublisher
Wiley-V C H Verlag GmbhPublication status
- Published
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Po Box 10 11 61, Weinheim, Germany, D-69451Socio-economic Objectives
200199 Clinical health not elsewhere classifiedUsage metrics
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