title: TLR5 mediates CD172α(+) intestinal lamina propria dendritic cell induction of Th17 cells.
abstract: Multiple mechanisms exist in regulation of host responses to massive challenges from microbiota to maintain immune homeostasis in the intestines. Among these is the enriched Th17 cells in the intestines, which regulates intestinal homeostasis through induction of antimicrobial peptides and secretory IgA among others. However, the means by which Th17 cells develop in response to microbiota is still not completely understood. Although both TLR5 and CD172α(+) lamina propria dendritic cells (LPDC) have been shown to promote Th17 cell development, it is still unclear whether TLR5 mediates the CD172α(+)LPDC induction of Th17 cells. By using a microbiota antigen-specific T cell reporter mouse system, we demonstrated that microbiota antigen-specific T cells developed into Th17 cells in the intestinal LP, but not in the spleen when transferred into TCRβxδ(-/-) mice. LPDCs expressed high levels of TLR5, and most CD172α(+)LPDCs also co-expressed TLR5. LPDCs produced high levels of IL-23, IL-6 and TGFβ when stimulated with commensal flagellin and promoted Th17 cell development when cultured with full-length CBir1 flagellin but not CBir1 peptide. Wild-type CD172α(+), but not CD172α(-), LPDCs induced Th17 cells, whereas TLR5-deficient LPDC did not induce Th17 cells. Our data thereby demonstrated that TLR5 mediates CD172α(+)LPDC induction of Th17 cells in the intestines.
authors.affiliation: Department of Gastroenterology, The Qilu Hospital, Shandong University, Shandong, China.|Department of Microbiology and Immunology, and University of Texas Medical Branch, USA.
authors.forename: Han
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Pathology, University of Texas Medical Branch, USA.
authors.forename: Feidi
authors.initials: F
authors.lastname: Chen
authors.affiliation: Department of Microbiology and Immunology, and University of Texas Medical Branch, USA.|Department of Gastroenterology, The Shanghai Tenth People's Hospital, Tongji University, Shanghai, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wu
authors.affiliation: Department of Microbiology and Immunology, and University of Texas Medical Branch, USA.
authors.forename: Anthony T
authors.initials: AT
authors.lastname: Cao
authors.affiliation: Department of Microbiology and Immunology, and University of Texas Medical Branch, USA.|Department of Biopharmaceutics, School of Pharmacy, Fourth Military Medical University, Xi'an, China.
authors.forename: Xiaochang
authors.initials: X
authors.lastname: Xue
authors.affiliation: Department of Microbiology and Immunology, and University of Texas Medical Branch, USA.
authors.forename: Suxia
authors.initials: S
authors.lastname: Yao
authors.affiliation: Department of Microbiology and Immunology, and University of Texas Medical Branch, USA.
authors.forename: Heather L
authors.initials: HL
authors.lastname: Evans-Marin
authors.affiliation: Department of Gastroenterology, The Qilu Hospital, Shandong University, Shandong, China.
authors.forename: Yan-Qing
authors.initials: YQ
authors.lastname: Li
authors.affiliation: Department of Microbiology and Immunology, and University of Texas Medical Branch, USA.|Department of Pathology, University of Texas Medical Branch, USA.
authors.forename: Yingzi
authors.initials: Y
authors.lastname: Cong
mesh_terms: D000818:Animals; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D005408:Flagellin / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000276:immunology; D006706:Homeostasis; D018928:Immunity, Mucosal; D053759:Interleukin-23 / Q000235:genetics / Q000276:immunology; D015850:Interleukin-6 / Q000235:genetics / Q000276:immunology; D007413:Intestinal Mucosa / Q000166:cytology / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D061251:Primary Cell Culture; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000172:deficiency / Q000235:genetics / Q000276:immunology; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000172:deficiency / Q000235:genetics / Q000276:immunology; D011971:Receptors, Immunologic / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D015398:Signal Transduction; D058504:Th17 Cells / Q000166:cytology / Q000276:immunology*; D051198:Toll-Like Receptor 5 / Q000235:genetics / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000276:immunology
chemical_list: C502160:CBir1 flagellin; D053759:Interleukin-23; D015850:Interleukin-6; C501922:Sirpa protein, mouse; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta; D011971:Receptors, Immunologic; D051198:Toll-Like Receptor 5; D016212:Transforming Growth Factor beta; D005408:Flagellin