Role of KLF2 and KLF3 in balancing recirculating and resident memory fates 2993

Abstract Description Differentiation of CD8 T cells from naïve to effector to memory cells is a crucial process for pathogen clearance and long-term protection. There are key transcription factors and trafficking molecules associated with this differentiation process, including Krüppel-like factors 2 (KLF2), which regulates migration via Sphingosine-1-phosphate receptor 1 (S1PR1), and closely related KLF3. KLF2 is necessary for CD8 T cells to migrate, but in an S1PR1 independent manner, suggesting KLF2’s impact on CD8 differentiation may extent beyond trafficking control. My research examines KLF2 and KLF3 in memory T cell differentiation. Using CRISPR/Cas9 to ablate KLF2 or KLF3 in P14 CD8 T cells, I observed that KLF2-deficient cells quickly lose recirculation capacity and acquire tissue-resident traits very quickly following infection. Transcriptionally we observed expression changes of other TFs known to drive residency and recirculation programs, such as Hobit (up), Tbet (down), Zeb2 (down), and KLF3 (down) suggesting that KLF2 could play a pivotal role in memory differentiation programs. KLF3-deficient cells had enhanced circulating memory traits suggesting that KLF3 may suppress KLF2 and influence CD8 memory differentiation. These findings position KLF2 and KLF3 as central regulators in CD8 T cell fate decisions, potentially leading to applications in vaccine development and immunotherapy by targeting immune memory and response regulation. Funding Sources NIH AI188630 Topic Categories Lymphocyte Differentiation and Peripheral Maintenance (LYM)