regulation of toll-like receptor 5 gene expression and function on mucosal dendritic cellstoll样受体调节5粘膜树突状细胞基因表达和功能.pdfVIP

Regulation of Toll-like Receptor 5 Gene Expression and Function on Mucosal Dendritic Cells Ting Feng1,2, Yingzi Cong1,2,3, Katie Alexander1,2, Charles O. Elson1,2* 1 Department of Microbiology, University of Alabama at Birmingham, Birmingham, Alabama, United States of America, 2 Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, United States of America, 3 Departments of Microbiology/Immunology and Pathology, University of Texas Medical Branch, Galveston, Texas, United States of America Abstract Toll-like receptor (TLR) 5 has been shown to maintain intestinal homeostasis and regulate host defense against enterobacterial infection. However, how TLR5 expression is regulated and its function in the intestine have not been fully elucidated. Here we demonstrate that mucosal dendritic cells (DCs), but not splenic DCs, express high levels of TLR5 protein. Alternatively spliced Tlr5 transcripts were identified but it did not explain the selective expression of TLR5 on mucosal DCs. Treatment with various bacterial ligands downregulated BMDC TLR5 expression, while retinoic acid and host stromal cell- derived signals promoted TLR5 expression in a TGF-b-independent mechanism. Signaling through TLR5 restrained regulatory T (Treg) cell generation, and accordingly, TLR52/ 2 mice displayed increased frequencies of Foxp3+ Treg cells in the intestinal lamina propria. Our data indicate that bacterial and host factors differentially regulate DC TLR5 expression. TLR5 signaling regulates immune responses towards the microbiota via modulation of the Treg/effector T cell balance. Citation: Feng T, Cong Y, Alexander K, Elson CO (2012) Regulation of Toll-like Receptor 5 Gene Expression and Func