KLF2 Drives S1PR1 to Control Memory CD8 T Cell Migration and Tissue Residency

An expert lecture on ImmuneZoom explains how the transcription factor KLF2 drives expression of S1PR1 (sphingosine-1-phosphate receptor 1), controlling whether mature T cells leave the thymus and secondary lymphoid organs to enter blood circulation. CRISPR screens in P14 TCR transgenic mice during acute LCMV infection showed that KLF2 deficiency shifts T cell distribution, reducing representation among small intestinal intraepithelial lymphocytes without causing cell death, partly compensated by S1PR5. KLF2 also regulates homing molecules such as CXCR3 and L-selectin (CD62L), informing work on tissue-resident memory T cell pools and PD-1 blockade.