The role of AP-1 and NFKB in the rapid recall ability of memory T cells 2138

Abstract Description Central and effector memory CD4 T cells are essential for long-lasting immunity to pathogens after a prior encounter. Unlike naïve, the memory cells possess rapid recall ability to quickly produce effector molecules in response to their antigen re-exposure. The molecular mechanism of the rapid recall response is not well understood. We have previously established that the rapid recall ability of memory T cells is associated with epigenetic gene poising. AP-1, NFAT and NFKB are key TFs induced by T cell activation. Upon cell stimulation they regulate transcription of immune response genes, and AP-1 is a key inducer of epigenetic changes in naïve T cells. I hypothesize that these activation-inducible TFs play a role in transcription of cytokines genes enabling rapid recall responses in memory T cells. In our preliminary ChIP-Seq data, we showed differential binding of AP-1 and NFKB at cytokine gene enhancers of Naïve and Memory cells. Further, I utilized A-FOS, a dominant negative AP-1 protein, and NFKB inhibitors in naïve, TCM and TEM cells to test the function of AP-1 and NFKB in these cell types. The cells were activated and subjected to ATAC and RNA-Seq. Upon stimulation, we observed a significant decrease of chromatin accessibility in A-FOS treated cells and expression of cytokine genes (IL2, IFNG) with IKB inhibition and A-FOS electroporation. Our results suggest AP-1 regulates chromatin accessibility, and AP-1 together with NFKB enhance immune response in memory T cells. Funding Sources NIH R01AI153442-01A1 Topic Categories Immune Response Regulation: Molecular Mechanisms (IRM)