Zhichao Lu, Jingwei Zhao, Jue Zhu, Chenxing Wang, Weiquan Liao, Xingjia Zhu, Qianqian Liu, Rui Jiang, Jiahua Qu, Yongqi Zhu, Lin Zhang, Kaijiang Kang, Ziheng Wang, Peipei Gong
Young patients with traumatic brain injury (TBI) have a better prognosis than the aged, but the underlying mechanisms are not clear. Here, we identified a population of IL-19+ monocytes derived from cranial bone marrow appearing in the brain after TBI. IL-19+ monocytes inhibit the glial hyper-response and promote neurological recovery after TBI through the IL-19/IL-20R axis, which is defective in aged patients. Further studies have proven that CX3CR1 on the IL-19+ monocytes is attracted by CX3CL1 after TBI, infiltrating the brain, and exerting immunoregulatory effects. Notably, intracerebroventricular injection of recombinant CX3CL1 inhibits excessive neuroinflammation and promotes neurological recovery of aged TBI mice by enhancing the output of cranial IL-19+ monocytes to the brain. Our study demonstrates the important involvement of cranial bone marrow in the repair process after TBI and suggests that the characteristic recruitment of cranial bone marrow-derived regulatory myeloid cells may be an effective approach to improve outcomes of aged TBI.