Cxcr4 and Cxcr6 Dually Limits T Cell Entry Into the Polyomavirus-infected Brain

Regulation of the T cell response during viral infection of the central nervous system (CNS) is a vital aspect of host response for pathogen clearance but must be tightly regulated as to prevent excess inflammation and pathology. Chemokines are often cited as the source for control of both the CD8 and CD4 T cell response, modulating their migration and proliferation. Here mouse polyomavirus (MuPyV) is used as in vivo model for JCPyV, the causative agent of Progressive Multifocal Leukoencephalopathy (PML), to investigate the duel control of CXCR4 and CXCR6 on brain T cells. MERFISH single cell spital transcriptomes for the first time reveals the full landscape of MuPyV brain infection and genetic knockout and small molecule antagonists models divulge the T cell response control mechanism. This work points to the potential of new duel targeting therapeutic strategies for PML patients and contributes to central details about the functions of CXCR4 and CXCR6 that are required for full understanding of T cell responses in the CNS. 2 samples underwent ICV sham (DMEM) injections, 2 samples underwent ICV MuPyV injections.