Bone marrow–derived emergency monopoiesis drives brain–lung axis injury after traumatic brain injury via IL-1

作者：Tianrui Ma, Jingjing Liu, Zhuyu Gao, Yang Li, Jie Lin, Kaifeng Pang, Rui Li, Xiaoyang Zhang, Lujia Tang, Yafan Liu, Hao Zhang, Yichi Zhang, Lorie Chen Cai, Zijian Zhou, Kaibin Shi, Tao Zhu, Jianning Zhang, Jieli Chen, Zhigang Cai, Ying Fu, Zilong Zhao · 发表于：Journal of Neuroinflammation · 年份：2025 · DOI：10.1186/s12974-025-03589-y · 被引用次数：8 · 研究领域：Neuroinflammation and Neurodegeneration Mechanisms、Traumatic Brain Injury and Neurovascular Disturbances、Immune Response and Inflammation

Traumatic brain injury (TBI) presents a major clinical burden, often resulting in both acute neurological impairment and pulmonary dysfunction, underscoring the complex and poorly understood brain-lung axis. Although dual-organ injury is well-documented, the mechanistic basis linking brain trauma to peripheral organ damage has remained elusive. In this study, we integrate clinical observations, single-cell RNA sequencing of skull bone marrow (BM) from TBI patients, and preclinical mouse models to uncover a rapid, IL-1-driven emergency monopoiesis response initiated within 24 h post-injury. We demonstrate that TBI induces accelerated, myeloid-skewed hematopoiesis in the cranial BM, marked by the expansion and mobilization of proinflammatory monocytes. This immune activation correlates strongly with both neurological decline and acute lung injury. Mechanistically, we identify IL-1 signaling as a master regulator of this pathological hematopoietic reprogramming. Disruption of IL-1R1 signaling, either globally or selectively within the hematopoietic compartment, attenuates emergency monopoiesis, preserves blood-brain barrier integrity, and reduces inflammatory infiltration in both the brain and lungs. These findings establish emergency monopoiesis as a central driver of multi-organ injury in TBI and reveal the BM niche as a critical yet underappreciated target in post-traumatic systemic pathology. By targeting IL-1R1-dependent hematopoietic activation, this study proposes a novel...