Depletion of Collagen IX Alpha1 Impairs Myeloid Cell Function

Probst, Kristina and Stermann, Jacek and von Bomhard, Inga and Etich, Julia and Pitzler, Lena and Niehoff, Anja and Bluhm, Bjoern and Xu, Haifeng C. and Lang, Philipp A. and Chmielewski, Markus and Abken, Hinrich and Blissenbach, Birgit and Machova, Alzbeta and Papadopoulou, Nikoletta and Brachvogel, Bent (2018) Depletion of Collagen IX Alpha1 Impairs Myeloid Cell Function. STEM CELLS, 36 (11). pp. 1752-1763. ISSN 1066-5099, 1549-4918

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Abstract

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

Item Type: Article
Uncontrolled Keywords: HEMATOPOIETIC STEM-CELLS; EXTRACELLULAR-MATRIX; LISTERIA-MONOCYTOGENES; PROGENITOR CELLS; IMMUNE-SYSTEM; CARTILAGE; BONE; MICE; MACROPHAGE; DIFFERENTIATION; Bone marrow; Collagen; Listeria; Matrix; Myeloid
Subjects: 600 Technology > 610 Medical sciences Medicine
Divisions: Medicine > Lehrstuhl für Immunologie
Depositing User: Dr. Gernot Deinzer
Date Deposited: 10 Oct 2019 09:32
Last Modified: 10 Oct 2019 09:32
URI: https://pred.uni-regensburg.de/id/eprint/13606

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