Soluble PD-L1 reprograms blood monocytes to prevent cerebral edema and facilitate recovery after ischemic stroke

• DOI: 10.1016/j.bbi.2023.12.007
• Publication Date: 2023-12-07T18:00:06Z
• Authors: Jennifer E. Kim; Ryan P. Lee; Eli Yazigi; Lyla Atta; James Feghali; Ayush Pant; Aanchal Jain; Idan Levitan; Eileen Kim; Kisha Patel; Nivedha Kannapadi; Pavan Shah; Adnan Bibic; Zhipeng Hou; Justin M. Caplan; L. Fernando Gonzalez; Judy Huang; Risheng Xu; Jean Fan; Betty Tyler; Henry Brem; Vassiliki A. Bous...; Lauren Jantzie; Shenandoah Robinson; Raymond C. Koehler; Michael Lim; Rafael J. Tamargo; Christopher M. Ja...
• Keywords: Monocyte; Stroke; Cerebral edema

Acute cerebral ischemia triggers a profound inflammatory response. While macrophages polarized to an M2-like phenotype clear debris and facilitate tissue repair, aberrant or prolonged macrophage activation is counterproductive recovery. The inhibitory immune checkpoint Programmed Cell Death Protein 1 (PD-1) upregulated on precursors (monocytes) in the blood after acute cerebrovascular injury. To investigate therapeutic potential of PD-1 activation, we immunophenotyped circulating monocytes from patients found that expression was period stroke. Murine studies using temporary middle artery (MCA) occlusion (MCAO) model showed intraperitoneal administration soluble Ligand-1 (sPD-L1) significantly decreased brain edema improved overall survival. Mice receiving sPD-L1 also had higher performance scores short-term, more closely resembled sham animals assessments long-term functional These clinical radiographic benefits were abrogated global myeloid-specific knockout animals, confirming PD-1+ as target sPD-L1. Single-cell RNA sequencing revealed treatment skewed monocyte maturation non-classical Ly6C