title: Lung dendritic cells induce migration of protective T cells to the gastrointestinal tract.
abstract: Developing efficacious vaccines against enteric diseases is a global challenge that requires a better understanding of cellular recruitment dynamics at the mucosal surfaces. The current paradigm of T cell homing to the gastrointestinal (GI) tract involves the induction of α4β7 and CCR9 by Peyer's patch and mesenteric lymph node (MLN) dendritic cells (DCs) in a retinoic acid-dependent manner. This paradigm, however, cannot be reconciled with reports of GI T cell responses after intranasal (i.n.) delivery of antigens that do not directly target the GI lymphoid tissue. To explore alternative pathways of cellular migration, we have investigated the ability of DCs from mucosal and nonmucosal tissues to recruit lymphocytes to the GI tract. Unexpectedly, we found that lung DCs, like CD103(+) MLN DCs, up-regulate the gut-homing integrin α4β7 in vitro and in vivo, and induce T cell migration to the GI tract in vivo. Consistent with a role for this pathway in generating mucosal immune responses, lung DC targeting by i.n. immunization induced protective immunity against enteric challenge with a highly pathogenic strain of Salmonella. The present report demonstrates novel functional evidence of mucosal cross talk mediated by DCs, which has the potential to inform the design of novel vaccines against mucosal pathogens.
authors: Laboratory of Cellular Immunology and Physiology and 2 Laboratory of Mucosal Immunology, The Rockefeller University, New York, NY 10065, USA.
authors: Darren
authors: D
authors: Ruane
authors: Lucas
authors: L
authors: Brane
authors: Bernardo Sgarbi
authors: BS
authors: Reis
authors: Cheolho
authors: C
authors: Cheong
authors: Jordan
authors: J
authors: Poles
authors: Yoonkyung
authors: Y
authors: Do
authors: Hongfa
authors: H
authors: Zhu
authors: Klara
authors: K
authors: Velinzon
authors: Jae-Hoon
authors: JH
authors: Choi
authors: Natalie
authors: N
authors: Studt
authors: Lloyd
authors: L
authors: Mayer
authors: Ed C
authors: EC
authors: Lavelle
authors: Ralph M
authors: RM
authors: Steinman
authors: Daniel
authors: D
authors: Mucida
authors: Saurabh
authors: S
authors: Mehandru
mesh_terms: D000281:Administration, Intranasal; D019264:Adoptive Transfer; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D000954:Antigens, Surface / Q000378:metabolism; D050976:Basic-Leucine Zipper Transcription Factors / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects / Q000276:immunology*; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D000068876:Fingolimod Hydrochloride; D041981:Gastrointestinal Tract / Q000187:drug effects / Q000276:immunology* / Q000382:microbiology / Q000473:pathology*; D018928:Immunity, Mucosal / Q000187:drug effects / Q000276:immunology*; D007114:Immunization; D016023:Integrins / Q000378:metabolism; D007413:Intestinal Mucosa / Q000187:drug effects / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D037181:Lectins, C-Type / Q000378:metabolism; D008168:Lung / Q000473:pathology*; D037241:Mannose-Binding Lectins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D011409:Propylene Glycols / Q000494:pharmacology; D054388:Receptors, CCR / Q000378:metabolism; D012475:Salmonella / Q000187:drug effects / Q000276:immunology; D012481:Salmonella Infections, Animal / Q000276:immunology / Q000382:microbiology / Q000473:pathology / Q000517:prevention & control; D015398:Signal Transduction / Q000187:drug effects; D013110:Sphingosine / Q000031:analogs & derivatives / Q000494:pharmacology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D014212:Tretinoin / Q000494:pharmacology
chemical_list: D015703:Antigens, CD; D000954:Antigens, Surface; D050976:Basic-Leucine Zipper Transcription Factors; C431772:Batf protein, mouse; C119309:CC chemokine receptor 9; C498497:Cd207 protein, mouse; D016023:Integrins; D037181:Lectins, C-Type; D037241:Mannose-Binding Lectins; D011409:Propylene Glycols; D054388:Receptors, CCR; D016212:Transforming Growth Factor beta; C071777:integrin alpha4beta7; D014212:Tretinoin; D000068876:Fingolimod Hydrochloride; D013110:Sphingosine
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