Tonsil-derived mesenchymal stromal cells produce CXCR2-binding chemokines and acquire follicular dendritic cell-like phenotypes under TLR3 stimulation |
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Affiliation: | 1. Department of Microbiology, School of Medicine, Ewha Womans University, Seoul 158-710, Republic of Korea;2. Department of Pediatrics, School of Medicine, Ewha Womans University, Seoul 158-710, Republic of Korea;1. Laboratorio de Bioquímica y Biología Molecular, Centro de Química del Instituto de Ciencias (ICUAP), Edificio 103F, Ciudad Universitaria, Benemérita Universidad Autónoma de Puebla, Puebla, Puebla, Mexico;2. Posgrado en Ciencias Químicas, Edificio FCQ10, Ciudad Universitaria, Benemérita Universidad Autónoma de Puebla, Puebla, Puebla, Mexico;3. Laboratorio de Biología Molecular y Virología, Centro de Investigación Biomédica de Oriente, Instituto Mexicano del Seguro Social, Hospital General de Zona No. 5, Km. 4.5 Carretera Federal Atlixco-Metepec, Metepec, Puebla, Mexico;4. Laboratorio de Virología, Instituto Nacional de Investigaciones Forestales, Agrícolas y Pecuarias. Km 15.5 Carretera México-Toluca, Palo Alto, Cuajimalpa, Distrito Federal, Mexico;1. Department of Neurosciences, Medical University of South Carolina, Charleston, SC, USA;2. Department of Comparative Medicine, Medical University of South Carolina, Charleston, SC, USA;1. Division of Rheumatology, 3rd Department of Internal Medicine, Medical University of Vienna, 18-20 Währinger Gürtel, 1090 Vienna, Austria;2. Division of Neuro- and Musculoskeletal Radiology, Department of Radiology and Nuclear Medicine, Medical University of Vienna, 18-20 Währinger Gürtel, 1090 Vienna, Austria;3. Department of Medicine, Endocrinology, Zealand University Hospital, Lykkebaekvej 1, 4600 Koege, Denmark;1. Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA;2. Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA |
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Abstract: | We previously isolated mesenchymal stromal cells from human tonsils (T-MSCs) and showed the potential of these cells to differentiate into the mesodermal lineage and acquire a follicular dendritic cell (FDC) phenotype under cytokine stimulation. Because these T-MSCs were originally isolated from inflamed tonsillar tissues, we were curious about their activation status in response to innate immune stimuli, such as Toll-like receptors (TLRs). Therefore, we analyzed the expression profile of TLRs in T-MSCs and stimulated the T-MSCs with TLR agonists. TLR3 stimuli induced C–C chemokine receptor type 6 expression in T-MSCs after 24 h. Furthermore, results from cytokine arrays showed increases in epithelial neutrophil-activating peptide-78/C-X-C motif chemokine (CXCL) 5, granulocyte chemotactic protein-2/CXCL6, growth-related oncogene-α/CXCL1, interleukin-8/CXCL8, and interferon gamma-induced protein-10/CXCL10. CD54 expression was also increased after TLR3 stimulation. However, co-culturing T-MSCs with human B cells did not induce B-cell proliferation. This suggests that TLR3 stimulates the differentiation of T-MSCs into FDC-like cells and induces chemokine secretion, possibly by recruiting C–X–C chemokine receptor 2-expressing immune cells. In addition, T-MSCs also appeared to exert immunomodulatory effects by inhibiting B-cell proliferation, possibly by down-regulating CD18. |
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Keywords: | Toll-like receptors Tonsil-derived mesenchymal stromal cells CXCR2 CD54 B cells |
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