Depletion of Collagen IX Alpha1 Impairs Myeloid Cell Function
Depletion of Collagen IX Alpha1 Impairs Myeloid Cell Function
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DOI：
10.1002/stem.2892
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发表时间：
2018-09
期刊：
影响因子：
5.2
通讯作者：
K. Probst;J. Stermann;Inga von Bomhard;J. Etich;Lena Pitzler;A. Niehoff;Björn Bluhm;Haifeng C. Xu;P. Lang;M. Chmielewski;H. Abken;Birgit Blissenbach;A. Machova;N. Papadopoulou;B. Brachvogel
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文献类型：
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作者：
K. Probst;J. Stermann;Inga von Bomhard;J. Etich;Lena Pitzler;A. Niehoff;Björn Bluhm;Haifeng C. Xu;P. Lang;M. Chmielewski;H. Abken;Birgit Blissenbach;A. Machova;N. Papadopoulou;B. Brachvogel
小梁细胞外基质(ECM)形成一个三维支架，稳定骨髓，为细胞-基质相互作用提供底物，并保留、呈现或释放信号以调节造血干细胞和祖细胞的发育。然而，关于骨小梁细胞外基质成分对造血的影响的研究很少。在IXAlpha1胶原缺失(Col9a1(−/−))小鼠中，我们发现IXAlpha1胶原缺乏导致富含纤维连接蛋白的无序小梁网络，并导致髓系细胞减少，同时骨髓单核细胞上集落刺激因子1受体表达减少。相比之下，骨髓中的B细胞数量和胸腺中的T细胞数量保持不变。骨髓微环境的改变不仅可能减少髓系细胞的数量，而且对髓系细胞的功能也有长期的影响。用单核细胞李斯特氏菌感染小鼠，分析其髓系细胞的功能。在这种情况下，在体内观察到Col9a1(−/−)小鼠对细菌感染的不充分的巨噬细胞依赖的清除。这主要是由于干扰素-γ/肿瘤坏死因子-α介导的巨噬细胞激活受损所致。因此，IXAlpha1胶原蛋白的丢失破坏了骨小梁网络的稳定性，损害了髓系细胞的分化，并影响了对李斯特菌的先天免疫反应。干细胞2018；36：1752-1763
The trabecular extracellular matrix (ECM) forms a three‐dimensional scaffold to stabilize the bone marrow, provide substrates for cell‐matrix interactions and retain, present or release signals to modulate hematopoietic stem and progenitor cell development. However, the impact of trabecular ECM components on hematopoiesis has been poorly studied. Using collagen IX alpha1 ‐ deficient (Col9a1(−/−)) mice, we revealed that a lack of collagen IX alpha1 results in a disorganized trabecular network enriched in fibronectin, and in a reduction in myeloid cells, which was accompanied by a decrease in colony‐stimulating factor 1 receptor expression on monocytes from the bone marrow. In contrast, B‐cell numbers in the bone marrow and T‐cell numbers in the thymus remained unchanged. Alterations in the bone marrow microenvironment may not only reduce myeloid cell numbers, but also have long‐term implications for myeloid cell function. Mice were infected with Listeria moncytogenes to analyze the function of myeloid cells. In this case, an inadequate macrophage‐dependent clearance of bacterial infections was observed in Col9a1(−/−) mice in vivo. This was mainly caused by an impaired interferon‐gamma/tumor necrosis factor‐alpha‐mediated activation of macrophages. The loss of collagen IX alpha1 therefore destabilizes the trabecular bone network, impairs myeloid cell differentiation, and affects the innate immune response against Listeria. Stem Cells 2018;36:1752–1763