title: Goblet cells deliver luminal antigen to CD103+ dendritic cells in the small intestine.
abstract: The intestinal immune system is exposed to a mixture of foreign antigens from diet, commensal flora and potential pathogens. Understanding how pathogen-specific immunity is elicited while avoiding inappropriate responses to the background of innocuous antigens is essential for understanding and treating intestinal infections and inflammatory diseases. The ingestion of protein antigen can induce oral tolerance, which is mediated in part by a subset of intestinal dendritic cells (DCs) that promote the development of regulatory T cells. The lamina propria (LP) underlies the expansive single-cell absorptive villous epithelium and contains a large population of DCs (CD11c(+) CD11b(+) MHCII(+) cells) comprised of two predominant subsets: CD103(+) CX(3)CR1(-) DCs, which promote IgA production, imprint gut homing on lymphocytes and induce the development of regulatory T cells, and CD103(-) CX(3)CR1(+) DCs (with features of macrophages), which promote tumour necrosis factor-α (TNF-α) production, colitis, and the development of T(H)17 T cells. However, the mechanisms by which different intestinal LP-DC subsets capture luminal antigens in vivo remains largely unexplored. Using a minimally disruptive in vivo imaging approach we show that in the steady state, small intestine goblet cells (GCs) function as passages delivering low molecular weight soluble antigens from the intestinal lumen to underlying CD103(+) LP-DCs. The preferential delivery of antigens to DCs with tolerogenic properties implies a key role for this GC function in intestinal immune homeostasis.
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, St Louis, Missouri 63110, USA.
authors.forename: Jeremiah R
authors.initials: JR
authors.lastname: McDole
authors.forename: Leroy W
authors.initials: LW
authors.lastname: Wheeler
authors.forename: Keely G
authors.initials: KG
authors.lastname: McDonald
authors.forename: Baomei
authors.initials: B
authors.lastname: Wang
authors.forename: Vjollca
authors.initials: V
authors.lastname: Konjufca
authors.forename: Kathryn A
authors.initials: KA
authors.lastname: Knoop
authors.forename: Rodney D
authors.initials: RD
authors.lastname: Newberry
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Miller
mesh_terms: D000818:Animals; D000941:Antigens / Q000276:immunology* / Q000378:metabolism; D015703:Antigens, CD / Q000378:metabolism*; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D004032:Diet; D020397:Goblet Cells / Q000276:immunology* / Q000378:metabolism; D006706:Homeostasis; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology*; D007070:Immunoglobulin A / Q000276:immunology; D039001:Integrin alpha Chains / Q000378:metabolism*; D007421:Intestine, Small / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D036641:Microscopy, Fluorescence, Multiphoton; D012995:Solubility; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D058504:Th17 Cells / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
chemical_list: D000941:Antigens; D015703:Antigens, CD; D007070:Immunoglobulin A; D039001:Integrin alpha Chains; D014409:Tumor Necrosis Factor-alpha; C091367:alpha E integrins