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Goblet cells deliver luminal antigen to CD103+ dendritic cells in the small intestine
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Journal Article
Goblet cells deliver luminal antigen to CD103+ dendritic cells in the small intestine
2012
Overview
Goblet cells in the small intestine act as passages delivering small antigens to tolerance-inducing dendritic cells in the lamina propria.
Striking an immunological balance in the small intestine
How the balance between tolerance and immunity is maintained is an important question in immunology, and is of particular relevance to the small intestine, where innocuous antigens from the diet and potential pathogens are encountered simultaneously. McDole
et al
. show that goblet cells in the epithelium of the small intestine act as conduits through which small luminal antigens can be delivered to tolerance-inducing dendritic cells in the lamina propria, a layer of connective tissue beneath the epithelium. Through this mechanism, goblet cells could play a key part in promoting intestinal immune homeostasis.
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
+
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
2
,
3
,
4
,
5
,
6
,
7
,
8
,
9
, 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
5
,
6
,
7
,
10
. 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.
Publisher
Nature Publishing Group UK
Subject
/ Animals
/ Dendritic Cells - immunology
/ Dendritic Cells - metabolism
/ Diet
/ Humanities and Social Sciences
/ Humans
/ Immune Tolerance - immunology
/ Immunoglobulin A - immunology
/ Integrin alpha Chains - metabolism
/ Intestine, Small - immunology
/ Intestine, Small - metabolism
/ letter
/ Mice
/ Microscopy, Fluorescence, Multiphoton
/ Science
