Programmed Death 1 Deficiency Induces the Polarization of Macrophages/Microglia to the M1 Phenotype After Spinal Cord Injury in Mice

• DOI: 10.1007/s13311-013-0254-x
• Publication Date: 2014-05-22T13:25:48Z
• Authors: Anhui Yao; Fangfang Liu; Kun Chen; Liang Tang; Ling Liu; Kun Zhang; Caiyong Yu; Ganlan Bian; Hongmin Guo; Jingjing Zheng; Peng Cheng; Gong Ju; Jian Wang
• Keywords: Macrophage polarization; STAT1; Proinflammatory cytokine

The inflammatory response following spinal cord injury (SCI) involves the activation of resident microglia and infiltration macrophages. Macrophages can be polarized into classically activated proinflammatory M1 phenotype or alternatively anti-inflammatory M2 phenotype. Programmed cell death 1 (PD-1) is a critical immune inhibitory receptor involved in innate adaptive responses. However, whether PD-1 modulation macrophage/microglial polarization unknown. In this study, mRNA levels pd1 gradually increased after SCI, protein was found macrophages/microglia injured sections. knockout (KO) mice showed poor locomotor recovery crushing compared with wild-type mice. M1-type accumulated greater numbers PD-1-KO Under stimulation, induced expression occurred cultured macrophages microglia. suppressed by reducing phosphorylation signal transducer activator transcription (STAT1) promoted increasing STAT6 phosphorylation. mice, enhanced via STAT1 nuclear factor-kappa B. Furthermore, played various roles phagocytosis Therefore, our results suggest that signaling plays an important role regulation polarization. Thus, deregulated may induce toward Overall, provide new insights modulatory mechanisms polarization, thereby possibly facilitating development therapies for SCI through signaling.