Goblet cells deliver luminal antigen to CD103+ dendritic cells in the small intestine
| Autor: | Jeremiah R. McDole, Kathryn A. Knoop, Baomei Wang, Mark J. Miller, Keely G. McDonald, Rodney D. Newberry, Vjollca Konjufca, Leroy W. Wheeler |
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| Rok vydání: | 2012 |
| Předmět: |
Immunoglobulin A
CD11c Mice Transgenic chemical and pharmacologic phenomena T-Lymphocytes Regulatory Article Immune tolerance Mice 03 medical and health sciences 0302 clinical medicine Immune system Antigen Antigens CD Intestine Small Immune Tolerance medicine Homeostasis Animals Humans Antigens 030304 developmental biology 0303 health sciences Lamina propria Multidisciplinary biology Tumor Necrosis Factor-alpha hemic and immune systems Dendritic Cells Small intestine Diet 3. Good health Microscopy Fluorescence Multiphoton medicine.anatomical_structure Solubility 030220 oncology & carcinogenesis Immunology biology.protein Th17 Cells Tumor necrosis factor alpha Goblet Cells Integrin alpha Chains |
| Zdroj: | Nature |
| ISSN: | 1476-4687 0028-0836 |
| DOI: | 10.1038/nature10863 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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