The lymphotoxin-β receptor induces different patterns of gene expression via two NF-κB pathways

Emmanuel Dejardin, Nathalie M. Droin, Mireille Delhase, Elvira Haas, Yixue Cao, Constantin Makris, Zhi Wei Li, Michael Karin, Carl F. Ware, Douglas R. Green

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802 Citations (Scopus)

Abstract

The lymphotoxin-β receptor (LTβR) plays critical roles in inflammation and lymphoid organogenesis through activation of NF-κB. In addition to activation of the classical NF-κB, ligation of this receptor induces the processing of the cytosolic NF-κB2/p100 precursor to yield the mature p52 subunit, followed by translocation of p52 to the nucleus. This activation of NF-κB2 requires NIK and IKKα, while NEMO/IKKγ is dispensable for p100 processing. IKKβ-dependent activation of canonical NF-κB is required for the expression but not processing of p100 and for the expression of proinflammatory molecules including VCAM-1, MIP-1β, and MIP-2 in response to LTβR ligation. In contrast, IKKα controls the induction by LTβR ligation of chemokines and cytokines involved in lymphoid organogenesis, including SLC, BLC, ELC, SDF1, and BAFF.

Original languageEnglish
Pages (from-to)525-535
Number of pages11
JournalImmunity
Volume17
Issue number4
DOIs
Publication statusPublished - 1 Oct 2002
Externally publishedYes

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