The interleukin-4/PPAR γ signaling axis promotes oligodendrocyte differentiation and remyelination after brain injury

by Qingxiu Zhang, Wen Zhu, Fei Xu, Xuejiao Dai, Ligen Shi, Wei Cai, Hongfeng Mu, T. Kevin Hitchens, Lesley M. Foley, Xiangrong Liu, Fang Yu, Jie Chen, Yejie Shi, Rehana K. Leak, Yanqin Gao, Jun Chen, Xiaoming Hu The repair of white matter damage is of paramount importance for functional recovery after brain injuries. Here, we report that interleukin-4 (IL-4) promotes oligodendrocyte regeneration and remyelination. IL-4 receptor expression was detected in a variety of glial cells after ischemic brain injur y, including oligodendrocyte lineage cells. IL-4 deficiency in knockout mice resulted in greater deterioration of white matter over 14 d after stroke. Consistent with these findings, intranasal delivery of IL-4 nanoparticles after stroke improved white matter integrity and attenuated long-term senso rimotor and cognitive deficits in wild-type mice, as revealed by histological immunostaining, electron microscopy, diffusion tensor imaging, and electrophysiology. The selective effect of IL-4 on remyelination was verified in an ex vivo organotypic model of demyelination. By leveraging primary oligo dendrocyte progenitor cells (OPCs), microglia-depleted mice, and conditional OPC-specific peroxisome proliferator-activated receptor gamma (PPARĪ³) knockout mice, we discovered a direct salutary effect of IL-4 on oligodendrocyte differentiation that was mediated by the PPARĪ³ axis. Our findings reve al a new regenerative role of IL-4 in the central nervous system (CNS), which lies be...
Source: PLoS Biology: Archived Table of Contents - Category: Biology Authors: Source Type: research