NUDT2 Disruption Elevates Diadenosine Tetraphosphate (Ap(4)A) and Down-Regulates Immune Response and Cancer Promotion Genes

Marriott, Andrew S.; Vasieva, Olga; Fang, Yongxiang; Copeland, Nikki A.; McLennan, Alexander G.; Jones, Nigel J.

Nevertheless, in addition to MHC-II, a number of other genes involved in promotion of aspects of the adaptive immune response are up-regulated in NuKO cells. OX40 (CD134, TNFRSF4) is a member of the TNF receptor superfamily expressed by activated T helper cells and other cells and when engaged by the OX40L ligand promotes the clonal expansion of effector and memory T cells responding to an antigen [63] . It is up-regulated 5-fold. CD86 (up 2.2-fold) is expressed on antigen-presenting cells and interacts with T cell surface ligands. It is crucial for effective T cell activation and survival [64] and several studies have shown that down-regulation or blockade of CD86 can improve allograft survival [65] . FCER1G (up 8-fold) encodes the γ chain (FcRγ) of the high affinity IgE receptor FCεR1 [66] . FcRγ is also a component of several other Fc receptors and the T-cell receptor, which may explain its association by IPA 1 with several immune functions. Interestingly, activation of mast cells by aggregation of FCεR1 with IgE-antigen complexes has been reported to promote synthesis of Ap 4 A by lysyl-tRNA synthetase and the consequent transcriptional changes [10, 31, 36] . Up-regulation of FCER1G might therefore provide a mechanism to potentiate and prolong Ap 4 A synthesis.