Goblet cells deliver luminal antigen to [CD103.sup.+] dendritic cells in the small intestine

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 trea...

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Bibliographic Details
Published inNature (London) Vol. 483; no. 7389; pp. 345 - 350
Main Authors McDole, Jeremiah R, Wheeler, Leroy W, McDonald, Keely G, Wang, Baomei, Konjufca, Vjollca, Knoop, Kathryn A, Newberry, Rodney D, Miller, Mark J
Format Journal Article
LanguageEnglish
Published Nature Publishing Group 15.03.2012
Subjects
Antigens
Dendritic cells
Epithelial cells
Intestine, Small
Physiological aspects
T cells
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Summary: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 (1). The lamina propria (LP) underlies the expansive single-cell absorptive villous epithelium and contains a large population of DCs ([CD11c.sup.+] [CD11b.sup.+] [MHCII.sup.+] cells) comprised of two predominant subsets: [CD103.sup.+] [CX.sub.3][CR1.sup.-] DCs, which promote IgA production, imprint gut homing on lymphocytes and induce the development of regulatory T cells (2-9), and [CD103.sup.-] [CX.sub.3][CR1.sup.+] DCs (with features of macrophages), which promote tumour necrosis factor-a (TNF-a) production, colitis, and the development of [T.sub.H]17 T cells (5-7,10). However, the mechanisms by which different intestinal LP-DC subsets capture luminal antigens invivoremains 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.sup.+] LP-DCs. The preferential delivery of antigens to DCs with tolerogenic properties implies a key role for this GC function in intestinal immune homeostasis.
ISSN:0028-0836
1476-4687