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TLRs Regulate the Gatekeeping Functions of the Intestinal Follicle-Associated Epithelium

Sophie Chabot, Jessica S. Wagner, Stephanie Farrant and Marian R. Neutra
J Immunol April 1, 2006, 176 (7) 4275-4283; DOI: https://doi.org/10.4049/jimmunol.176.7.4275
Sophie Chabot
Department of Pediatrics, Harvard Medical School, GI Cell Biology Laboratory, Children’s Hospital Boston and Harvard Digestive Diseases Center, Boston, MA 02115
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Jessica S. Wagner
Department of Pediatrics, Harvard Medical School, GI Cell Biology Laboratory, Children’s Hospital Boston and Harvard Digestive Diseases Center, Boston, MA 02115
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Stephanie Farrant
Department of Pediatrics, Harvard Medical School, GI Cell Biology Laboratory, Children’s Hospital Boston and Harvard Digestive Diseases Center, Boston, MA 02115
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Marian R. Neutra
Department of Pediatrics, Harvard Medical School, GI Cell Biology Laboratory, Children’s Hospital Boston and Harvard Digestive Diseases Center, Boston, MA 02115
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Abstract

Initiation of adaptive mucosal immunity occurs in organized mucosal lymphoid tissues such as Peyer’s patches of the small intestine. Mucosal lymphoid follicles are covered by a specialized follicle-associated epithelium (FAE) that contains M cells, which mediate uptake and transepithelial transport of luminal Ags. FAE cells also produce chemokines that attract Ag-presenting dendritic cells (DCs). TLRs link innate and adaptive immunity, but their possible role in regulating FAE functions is unknown. We show that TLR2 is expressed in both FAE and villus epithelium, but TLR2 activation by peptidoglycan or Pam3Cys injected into the intestinal lumen of mice resulted in receptor redistribution in the FAE only. TLR2 activation enhanced transepithelial transport of microparticles by M cells in a dose-dependent manner. Furthermore, TLR2 activation induced the matrix metalloproteinase-dependent migration of subepithelial DCs into the FAE, but not into villus epithelium of wild-type and TLR4-deficient mice. These responses were not observed in TLR2-deficient mice. Thus, the FAE of Peyer’s patches responds to TLR2 ligands in a manner that is distinct from the villus epithelium. Intraluminal LPS, a TLR4 ligand, also enhanced microparticle uptake by the FAE and induced DC migration into the FAE, suggesting that other TLRs may modulate FAE functions. We conclude that TLR-mediated signals regulate the gatekeeping functions of the FAE to promote Ag capture by DCs in organized mucosal lymphoid tissues.

  • Received October 12, 2005.
  • Accepted January 26, 2006.
  • Copyright © 2006 by The American Association of Immunologists
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The Journal of Immunology: 176 (7)
The Journal of Immunology
Vol. 176, Issue 7
1 Apr 2006
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TLRs Regulate the Gatekeeping Functions of the Intestinal Follicle-Associated Epithelium
Sophie Chabot, Jessica S. Wagner, Stephanie Farrant, Marian R. Neutra
The Journal of Immunology April 1, 2006, 176 (7) 4275-4283; DOI: 10.4049/jimmunol.176.7.4275

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TLRs Regulate the Gatekeeping Functions of the Intestinal Follicle-Associated Epithelium
Sophie Chabot, Jessica S. Wagner, Stephanie Farrant, Marian R. Neutra
The Journal of Immunology April 1, 2006, 176 (7) 4275-4283; DOI: 10.4049/jimmunol.176.7.4275
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