Regulation of the PKCΘ-NF-κB axis int lymphocytes by the tumor necrosis factor receptor family member OX40

Takanori So, Michael Croft

Research output: Contribution to journalReview articlepeer-review

19 Citations (Scopus)


Antigen primed T lymphocytes need to expand and persist to promote adaptive immunity. The growth and survival signals that control this are in large part provided by the NF-κB pathway in activated or effector/memory T cells. Although several membrane receptors impact NF-κB activation, signaling from OX40 (CD134, TNFRSF4), a member of the tumor necrosis factor receptor (TNFR) superfamily, has proven to be important for T cell immunity and a strong contributor to NF-κB activity. PKCΘ directs the T cell receptor (TCR) and CD28-dependent assembly of a CBM complex (CARMA1, BCL10, and MALT1) for efficient activation of NF-κB, raising the question of whether other membrane bound receptors that activate NF-κB also require this PKCΘ-CBM axis to control TCR-independent T cell activity. We discuss here our recent data demonstrating that after ligation by OX40L (CD252, TNFSF4) expressed on antigen-presenting cells, OX40 translocates into detergent-insoluble membrane lipid microdomains (DIM or lipid rafts) inT cells irrespective ofTCR signals, and assembles into a signaling complex containing PKCΘ, together withTRAF2, RIP1, the CBM complex, and the IKKα/β/γ complex. PKCΘ is required for optimal NF-κB activation mediated by OX40 and thus works as an essential component of this OX40 signalosome. We also discuss the likelihood that other TNFR superfamily molecules might complex with PKCΘ in T cells, and whether PKC isoforms may be critical to the function of TNFR molecules in general.

Original languageEnglish
Article numberArticle 133
JournalFrontiers in immunology
Issue numberMAY
Publication statusPublished - 2012


  • CBM
  • IKK
  • NF-κB
  • OX40
  • PKCΘ
  • TRAF

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


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