Skull bone marrow-derived immune cells infiltrate the injured cerebral cortex and exhibit anti-inflammatory properties

IF 8.8 2区 医学 Q1 IMMUNOLOGY
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Abstract

Identifying the origins and contributions of peripheral-derived immune cell populations following brain injury is crucial for understanding their roles in neuroinflammation and tissue repair. This study investigated the infiltration and phenotypic characteristics of skull bone marrow-derived immune cells in the murine brain after traumatic brain injury (TBI). We performed calvarium transplantation from GFP donor mice and subjected the recipients to controlled cortical impact (CCI) injury 14 days post-transplant. Confocal imaging at 3 days post-CCI revealed GFP+ calvarium-derived cells were present in the ipsilateral injured cortex, expressing CD45 and CD11b immune markers. These cells included Ly6G-positive neutrophil or Ccr2-positive monocyte identities. Calvarium-derived GFP+/Iba1+ monocyte/macrophages expressed the efferocytosis receptor MERTK and displayed engulfment of NeuN+ and cleaved caspase 3+ apoptotic cells. Phenotypic analysis showed that greater calvarium-derived monocytes/macrophages disproportionately express the anti-inflammatory arginase-1 marker than pro-inflammatory CD86. To differentiate the responses of blood- and calvarium-derived macrophages, we transplanted GFP calvarium skull bone into tdTomato bone marrow chimeric mice, then performed CCI injury 14 days post-transplant. Calvarium-derived GFP+cells predominantly infiltrated the lesion boundary, while blood-derived tdTomato+ cells dispersed throughout the lesion and peri-lesion. Compared to calvarium-derived cells, more blood-derived cells expressed pro-inflammatory CD86 and displayed altered 3D morphologic traits. These findings uniquely demonstrate that skull bone marrow-derived immune cells infiltrate the brain after injury and contribute to the neuroinflammatory milieu, representing a novel immune cell source that may be further investigated for their causal role in functional outcomes.

颅骨骨髓免疫细胞渗入受伤的大脑皮层并表现出抗炎特性
确定脑损伤后外周源性免疫细胞群的起源和贡献对于了解它们在神经炎症和组织修复中的作用至关重要。本研究调查了创伤性脑损伤(TBI)后颅骨骨髓衍生免疫细胞在小鼠大脑中的浸润和表型特征。我们从 GFP 供体小鼠进行了颅骨移植,并在移植后 14 天对受体进行了受控皮质冲击(CCI)损伤。CCI后3天的共聚焦成像显示,同侧损伤皮层中存在GFP+钙灶衍生细胞,表达CD45和CD11b免疫标记。这些细胞包括Ly6G阳性的中性粒细胞或Ccr2阳性的单核细胞。钙源GFP+/Iba1+单核细胞/巨噬细胞表达出细胞吞噬受体MERTK,并吞噬NeuN+和裂解卡巴酶3+凋亡细胞。表型分析表明,与促炎性 CD86 相比,更多的钙源单核细胞/巨噬细胞不成比例地表达抗炎性精氨酸酶-1 标记。为了区分血液和钙颅源性巨噬细胞的反应,我们将 GFP 钙颅骨移植到tdTomato 骨髓嵌合小鼠体内,然后在移植后 14 天进行 CCI 损伤。颅骨来源的 GFP+ 细胞主要浸润病变边界,而血液来源的 tdTomato+ 细胞则分散在整个病变和病变周围。与钙源细胞相比,更多的血源细胞表达促炎性 CD86,并显示出改变的三维形态特征。这些研究结果独特地证明了颅骨骨髓来源的免疫细胞在损伤后浸润大脑并导致神经炎症环境,是一种新的免疫细胞来源,可进一步研究其在功能结果中的因果作用。
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来源期刊
CiteScore
29.60
自引率
2.00%
发文量
290
审稿时长
28 days
期刊介绍: Established in 1987, Brain, Behavior, and Immunity proudly serves as the official journal of the Psychoneuroimmunology Research Society (PNIRS). This pioneering journal is dedicated to publishing peer-reviewed basic, experimental, and clinical studies that explore the intricate interactions among behavioral, neural, endocrine, and immune systems in both humans and animals. As an international and interdisciplinary platform, Brain, Behavior, and Immunity focuses on original research spanning neuroscience, immunology, integrative physiology, behavioral biology, psychiatry, psychology, and clinical medicine. The journal is inclusive of research conducted at various levels, including molecular, cellular, social, and whole organism perspectives. With a commitment to efficiency, the journal facilitates online submission and review, ensuring timely publication of experimental results. Manuscripts typically undergo peer review and are returned to authors within 30 days of submission. It's worth noting that Brain, Behavior, and Immunity, published eight times a year, does not impose submission fees or page charges, fostering an open and accessible platform for scientific discourse.
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