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Publication : PRAT4A-dependent expression of cell surface TLR5 on neutrophils, classical monocytes and dendritic cells.

First Author  Shibata T Year  2012
Journal  Int Immunol Volume  24
Issue  10 Pages  613-23
PubMed ID  22836022 Mgi Jnum  J:188000
Mgi Id  MGI:5438883 Doi  10.1093/intimm/dxs068
Citation  Shibata T, et al. (2012) PRAT4A-dependent expression of cell surface TLR5 on neutrophils, classical monocytes and dendritic cells. Int Immunol 24(10):613-23
abstractText  AbstractToll-like receptor 5 (TLR5), a sensor for bacterial flagellin, mounts innate and adaptive immune responses, and has been implicated in infectious diseases, colitis and metabolic syndromes. Although TLR5 is believed to belong to cell surface TLRs, cell surface expression has never been verified. Moreover, it has remained unclear which types of immune cells express TLR5 and contribute to flagellin-dependent responses. In this study we established an anti-mouse TLR5 monoclonal antibody and studied the cell surface expression of TLR5 on immune cells. The macrophage cell line J774 expressed endogenous TLR5 on the cell surface and produced IL-6 and G-CSF in response to flagellin. Cell surface expression of TLR5 and flagellin-induced responses were completely abolished by silencing a TLR-specific chaperone protein associated with TLR4 A (PRAT4A), demonstrating that TLR5 is another client of PRAT4A. In the in vivo immune cells, cell surface TLR5 was mainly found on neutrophils and CD11b ( hi ) Ly6C ( hi ) classical monocytes in the bone marrow, circulation, spleen and inflammatory lesions. Ly6C ( hi ) classical monocytes, but not neutrophils, produced cytokines in response to flagellin. Splenic CD8 ( - ) CD4 ( + ) conventional dendritic cells and CD11c ( hi ) CD11b ( hi ) lamina propria DCs, also clearly expressed cell surface TLR5. Collectively, cell surface expression of TLR5 is dependent on PRAT4A and restricted to neutrophils, classical monocytes and specific DC subsets.
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