Goblet cells deliver luminal antigen to CD103+ DCs 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 tre...
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Published in | Nature (London) Vol. 483; no. 7389; pp. 345 - 349 |
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Main Authors | , , , , , , , |
Format | Journal Article |
Language | English |
Published |
14.03.2012
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Online Access | Get full text |
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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
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
–
9
, and CD103
−
CX
3
CR1
+
DCs (with features of macrophages), which promote TNFα production, colitis, and the development of Th17 T cells
5
–
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. |
---|---|
AbstractList | 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
–
9
, and CD103
−
CX
3
CR1
+
DCs (with features of macrophages), which promote TNFα production, colitis, and the development of Th17 T cells
5
–
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. |
Author | McDonald, Keely G. Konjufca, Vjollca Knoop, Kathryn A. Wheeler, Leroy W. Newberry, Rodney D. Wang, Baomei McDole, Jeremiah R. Miller, Mark J. |
AuthorAffiliation | 2 Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA 3 Department of Microbiology, Southern Illinois University, Carbondale, IL 62901 1 Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA |
AuthorAffiliation_xml | – name: 2 Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA – name: 1 Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA – name: 3 Department of Microbiology, Southern Illinois University, Carbondale, IL 62901 |
Author_xml | – sequence: 1 givenname: Jeremiah R. surname: McDole fullname: McDole, Jeremiah R. organization: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA Department of Microbiology, Southern Illinois University, Carbondale, IL 62901 – sequence: 2 givenname: Leroy W. surname: Wheeler fullname: Wheeler, Leroy W. organization: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA Department of Microbiology, Southern Illinois University, Carbondale, IL 62901 – sequence: 3 givenname: Keely G. surname: McDonald fullname: McDonald, Keely G. organization: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA Department of Microbiology, Southern Illinois University, Carbondale, IL 62901 – sequence: 4 givenname: Baomei surname: Wang fullname: Wang, Baomei organization: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA Department of Microbiology, Southern Illinois University, Carbondale, IL 62901 – sequence: 5 givenname: Vjollca surname: Konjufca fullname: Konjufca, Vjollca organization: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA Department of Microbiology, Southern Illinois University, Carbondale, IL 62901 – sequence: 6 givenname: Kathryn A. surname: Knoop fullname: Knoop, Kathryn A. organization: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA Department of Microbiology, Southern Illinois University, Carbondale, IL 62901 – sequence: 7 givenname: Rodney D. surname: Newberry fullname: Newberry, Rodney D. organization: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA Department of Microbiology, Southern Illinois University, Carbondale, IL 62901 – sequence: 8 givenname: Mark J. surname: Miller fullname: Miller, Mark J. organization: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA Department of Microbiology, Southern Illinois University, Carbondale, IL 62901 |
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Title | Goblet cells deliver luminal antigen to CD103+ DCs in the small intestine |
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