The role of AP-1 in the rapid recall ability of memory T cells.

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Presentation Time: 11:30 AM - 12:45 PM
Poster Board Number: B673
Abstract ID: 6461

Presenting Author:
Adenike R Shittu , Graduate Research Assistant at Cincinnati Children’s Hosp. Med. Ctr., Univ. of Cincinnati Col. of Med.

Abstract:

Central and effector memory CD4 T cells are essential for long-lasting immunity to pathogens after the initial encounter. Unlike naïve T cells, memory cells possess rapid recall ability to quickly produce effector molecules in response to re-exposure to their antigen. 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  is a key TF induced by T-cell activation. It is also the key inducer of epigenetic changes in naïve T cells upon activation. I hypothesize that AP-1 plays a role in the 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 at cytokine gene enhancers of Naïve and Memory T cells. Further, I utilized electroporation of a dominant negative AP-1 protein, A-FOS, into naïve, CM and EM T cells to test the function of AP-1 TF in these cell types. The cells were activated and subjected to ATAC and RNA-Seq. Upon stimulation, we observed a significant decrease in the accessibility and gene expression of cytokine genes in the cells electroporated with A-FOS treated compared to the GFP control. Our results show that AP-1 regulates chromatin accessibility and enhances immune responses in memory T cells. In the future, we will address the role of other activation-inducible TFs in directing rapid recall response.