title: Regulation of Toll-like receptor 5 gene expression and function on mucosal dendritic cells.
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-β-independent mechanism. Signaling through TLR5 restrained regulatory T (Treg) cell generation, and accordingly, TLR5(-/-) 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.
authors.affiliation: Department of Microbiology, University of Alabama at Birmingham, Birmingham, Alabama, United States of America.
authors.forename: Ting
authors.initials: T
authors.lastname: Feng
authors.forename: Yingzi
authors.initials: Y
authors.lastname: Cong
authors.forename: Katie
authors.initials: K
authors.lastname: Alexander
authors.forename: Charles O
authors.initials: CO
authors.lastname: Elson
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism* / Q000382:microbiology; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000276:immunology; D005786:Gene Expression Regulation; D007413:Intestinal Mucosa / Q000166:cytology*; D051379:Mice; D008810:Mice, Inbred C57BL; D013154:Spleen / Q000166:cytology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism; D051198:Toll-Like Receptor 5 / Q000235:genetics* / Q000276:immunology*; D016211:Transforming Growth Factor alpha / Q000276:immunology; D014212:Tretinoin / Q000276:immunology
chemical_list: D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D051198:Toll-Like Receptor 5; D016211:Transforming Growth Factor alpha; D014212:Tretinoin