Publication Date:
2012-03-17
Description:
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-alpha (TNF-alpha) 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.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3313460/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3313460/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉McDole, Jeremiah R -- Wheeler, Leroy W -- McDonald, Keely G -- Wang, Baomei -- Konjufca, Vjollca -- Knoop, Kathryn A -- Newberry, Rodney D -- Miller, Mark J -- AI077600/AI/NIAID NIH HHS/ -- AI083538/AI/NIAID NIH HHS/ -- AI095550/AI/NIAID NIH HHS/ -- DK064798/DK/NIDDK NIH HHS/ -- DK085941/DK/NIDDK NIH HHS/ -- P30 CA91842/CA/NCI NIH HHS/ -- P30-DK52574/DK/NIDDK NIH HHS/ -- R01 AI077600/AI/NIAID NIH HHS/ -- R01 AI077600-04/AI/NIAID NIH HHS/ -- R01 DK064798/DK/NIDDK NIH HHS/ -- R01 DK064798-08/DK/NIDDK NIH HHS/ -- R21 AI083538/AI/NIAID NIH HHS/ -- R21 AI083538-02/AI/NIAID NIH HHS/ -- U01 AI095550/AI/NIAID NIH HHS/ -- U01 AI095550-01/AI/NIAID NIH HHS/ -- England -- Nature. 2012 Mar 14;483(7389):345-9. doi: 10.1038/nature10863.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pathology and Immunology, Washington University School of Medicine, St Louis, Missouri 63110, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22422267" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Antigens/*immunology/metabolism
;
Antigens, CD/*metabolism
;
Dendritic Cells/cytology/*immunology/*metabolism
;
Diet
;
Goblet Cells/*immunology/metabolism
;
Homeostasis
;
Humans
;
Immune Tolerance/*immunology
;
Immunoglobulin A/immunology
;
Integrin alpha Chains/*metabolism
;
Intestine, Small/cytology/*immunology/metabolism
;
Mice
;
Mice, Transgenic
;
Microscopy, Fluorescence, Multiphoton
;
Solubility
;
T-Lymphocytes, Regulatory/immunology
;
Th17 Cells/immunology
;
Tumor Necrosis Factor-alpha/immunology
Print ISSN:
0028-0836
Electronic ISSN:
1476-4687
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
,
Natural Sciences in General
,
Physics
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