Tonsil-derived mesenchymal stromal cells produce CXCR2-binding chemokines and acquire follicular dendritic cell-like phenotypes under TLR3 stimulation

• Published in: Cytokine (Philadelphia, Pa.) Pa.), 2015-06, Vol.73 (2), p.225-235
• Main Authors: Ryu, Jung-Hwa, Park, Minhwa, Kim, Bo-Kyung, Ryu, Kyung-Ha, Woo, So-Youn
• Format: Article
• Language: English
• Subjects: B cells; B-Lymphocytes - cytology; B-Lymphocytes - metabolism; CD18 Antigens - metabolism; CD54; Cell Membrane - metabolism; Cell Proliferation; Chemokines - biosynthesis; Coculture Techniques; CXCR2; Dendritic Cells, Follicular - metabolism; Humans; Mesenchymal Stromal Cells - metabolism; Palatine Tonsil - cytology; Phenotype; Protein Binding; Receptors, Interleukin-8B - metabolism; RNA, Messenger - genetics; RNA, Messenger - metabolism; Toll-Like Receptor 3 - genetics; Toll-Like Receptor 3 - metabolism; Toll-Like Receptor 4 - metabolism; Toll-like receptors; Tonsil-derived mesenchymal stromal cells
• ISSN: 1043-4666; 1096-0023
• DOI: 10.1016/j.cyto.2015.02.028

Tonsil-derived mesenchymal stromal cells produce CXCR2-binding chemokines and inhibit B cell proliferation in vitro [Display omitted] •Tonsil-derived mesenchymal stromal cells (T-MSCs) produced CXCR2-binding chemokines upon TLR3 stimulation.•TLR3 stimulation induced CD54 expression on T-MSCs.•T-MSCs inhibited B cell proliferation in vitro. 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 24h. 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.