TY - JOUR
T1 - Regulation of the PKCΘ-NF-κB axis int lymphocytes by the tumor necrosis factor receptor family member OX40
AU - So, Takanori
AU - Croft, Michael
PY - 2012
Y1 - 2012
N2 - 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.
AB - 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.
KW - CBM
KW - IKK
KW - NF-κB
KW - OX40
KW - PKCΘ
KW - TNFRSF
KW - TNFSF
KW - TRAF
UR - http://www.scopus.com/inward/record.url?scp=84874039848&partnerID=8YFLogxK
U2 - 10.3389/fimmu.2012.00133
DO - 10.3389/fimmu.2012.00133
M3 - 総説
AN - SCOPUS:84874039848
SN - 1664-3224
VL - 3
JO - Frontiers in Immunology
JF - Frontiers in Immunology
IS - MAY
M1 - Article 133
ER -