Traumatic brain injury alters dendritic cell differentiation and distribution in lymphoid and non-lymphoid organs.
Traumatic brain injury alters dendritic cell differentiation and distribution in lymphoid and non-lymphoid organs.
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DOI：
10.1186/s12974-022-02609-5
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发表时间：
2022-10-01
影响因子：
9.3
通讯作者：
中科院分区：
文献类型：
--
作者：
创伤性脑损伤(TBI)介导的继发性损伤的病理生理后果尚不完全清楚。特别是，脑创伤对树突状细胞(DC)分化和维持的影响仍是完全未知的，树突状细胞被认为是免疫系统中最专业的抗原提呈细胞。在此，我们报道了颅脑损伤后第3天和第7天DC的分化、维持和功能发生改变。分别于伤后第1天、第3天、第7天从中度皮质损伤(CCI)或假手术组小鼠的长骨、脾、外周淋巴结(PLN)、肠系膜淋巴结(MLN)、肝、肺、皮肤和血液中采集标本。通过冲洗分离后肢胫骨和股骨的骨髓细胞。组织用胶原酶-D和DNA酶I消化，皮肤活检组织在解放酶 + DNA酶I的存在下消化，制成单细胞悬液，用氯化铵(干细胞技术)裂解红细胞，然后用70℃的μM尼龙网过滤。通过基于10色流式细胞术的免疫表型研究，鉴定骨髓组织的DC亚群和DC前体细胞。细胞内活性氧(ROS)通过H2DCFDA染色鉴定。我们的研究发现：(1)创伤后第3天和第7天，脾和骨髓中DC的频率和绝对数量发生改变；(2)参与DC抗原提呈的关键分子在创伤后第3天和第7天的表面表达受到影响；(3)创伤后循环和淋巴系统中组织特异性DC亚群的分布和功能失衡；(4)创伤后DC的早期分化程序，特别是造血干细胞对共同DC前体细胞(CDPs)的承诺被解除调控；(5)脑损伤后第3天和第7天，DC祖细胞和分化DC细胞内ROS水平降低。我们的数据首次表明，脑外伤影响DC的分布模式，并导致淋巴和非淋巴器官中DC亚群之间的失衡。此外，本研究表明，脑损伤后第3天和第7天DC的ROS水平降低，这可能解释了脑损伤后DC分化模式的改变。深入了解脑外伤后DC缺陷的分子机制对于治疗急性中枢神经系统损伤(如脑外伤、中风和脊髓损伤)患者的感染是必不可少的，也是有益的。
Pathophysiological consequences of traumatic brain injury (TBI) mediated secondary injury remain incompletely understood. In particular, the impact of TBI on the differentiation and maintenance of dendritic cells (DCs), which are regarded as the most professional antigen presenting cells of the immune system, remains completely unknown. Here, we report that DC-differentiation, maintenance and functions are altered on day 3 and day 7 after TBI. Long bones, spleen, peripheral lymph nodes (pLNs), mesenteric lymph nodes (mLNs), liver, lungs, skin and blood were collected from mice with either moderate-level cortical impact (CCI) or sham on day 1, day 3 or day 7 after TBI. Bone marrow cells were isolated from the tibias and femurs of hind limb through flushing. Tissues were digested with Collagenase-D and DNase I. Skin biopsies were digested in the presence of liberase + DNase I. Single cell suspensions were made, red blood cells were lysed with Ammonium chloride (Stem Cell Technology) and subsequently filtered using a 70 μM nylon mesh. DC subsets of the tissues and DC progenitors of the BM were identified through 10-color flow cytometry-based immunophenotyping studies. Intracellular reactive oxygen species (ROS) were identified through H2DCFDA staining. Our studies identify that; (1) frequencies and absolute numbers of DCs in the spleen and BM are altered on day 3 and day 7 after TBI; (2) surface expression of key molecules involved in antigen presentation of DCs were affected on day 3 and day 7 after TBI; (3) distribution and functions of tissue-specific DC subsets of both circulatory and lymphatic systems were imbalanced following TBI; (4) early differentiation program of DCs, especially the commitment of hematopoietic stem cells to common DC progenitors (CDPs), were deregulated after TBI; and (5) intracellular ROS levels were reduced in DC progenitors and differentiated DCs on day 3 and day 7 after TBI. Our data demonstrate, for the first time, that TBI affects the distribution pattern of DCs and induces an imbalance among DC subsets in both lymphoid and non-lymphoid organs. In addition, the current study demonstrates that TBI results in reduced levels of ROS in DCs on day 3 and day 7 after TBI, which may explain altered DC differentiation paradigm following TBI. A deeper understanding on the molecular mechanisms that contribute to DC defects following TBI would be essential and beneficial in treating infections in patients with acute central nervous system (CNS) injuries, such as TBI, stroke and spinal cord injury.
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影响因子：
9.3
作者：
Das M;Mohapatra S;Mohapatra SS
通讯作者：
Mohapatra SS
DOI：
10.1038/nri3477
发表时间：
2013-08
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
通讯作者：
--
影响因子：
6.7
作者：
Beshara R;Sencio V;Soulard D;Barthélémy A;Fontaine J;Pinteau T;Deruyter L;Ismail MB;Paget C;Sirard JC;Trottein F;Faveeuw C
通讯作者：
Faveeuw C
影响因子：
3.4
作者：
Hazeldine J;Lord JM;Belli A
通讯作者：
Belli A
影响因子：
1.8
作者：
Andraweera, Nalinda;Seemann, Richard
通讯作者：
Seemann, Richard