Interactions among secretory immunoglobulin A, CD71, and transglutaminase-2 affect permeability of intestinal epithelial cells to gliadin peptides

Corinne Lebreton, Sandrine Ménard, Juliette Abed, Ivan C. Moura, Rosanna Coppo, Christophe Dugave, Renato C. Monteiro, Aurélie Fricot, Meriem G. Traore, Martin Griffin, Christophe Cellier, Georgia Malamut, Nadine Cerf-Bensussan, Martine Heyman

Research output: Contribution to journalArticle

Abstract

BACKGROUND & AIMS: The transferrin receptor (CD71) is up-regulated in duodenal biopsy samples from patients with active celiac disease and promotes retrotransport of secretory immunolglobulin A (SIgA)-gliadin complexes. We studied intestinal epithelial cell lines that overexpress CD71 to determine how interactions between SIgA and CD71 promote transepithelial transport of gliadin peptides. METHODS: We analyzed duodenal biopsy specimens from 8 adults and 1 child with active celiac disease. Caco-2 and HT29-19A epithelial cell lines were transfected with fluorescence-labeled small interfering RNAs against CD71. Interactions among IgA, CD71, and transglutaminase 2 (Tgase2) were analyzed by flow cytometry, immunoprecipitation, and confocal microscopy. Transcytosis of SIgACD71 complexes and intestinal permeability to the gliadin 3H-p3149 peptide were analyzed in polarized monolayers of Caco-2 cells. RESULTS: Using fluorescence resonance energy transfer and in situ proximity ligation assays, we observed physical interactions between SIgA and CD71 or CD71 and Tgase2 at the apical surface of enterocytes in biopsy samples and monolayers of Caco-2 cells. CD71 and Tgase2 were co-precipitated with SIgA, bound to the surface of Caco-2 cells. SIgACD71 complexes were internalized and localized in early endosomes and recycling compartments but not in lysosomes. In the presence of celiac IgA or SIgA against p3149, transport of intact 3H-p3149 increased significantly across Caco-2 monolayers; this transport was inhibited by soluble CD71 or Tgase2 inhibitors. CONCLUSIONS: Upon binding to apical CD71, SIgA (with or without gliadin peptides) enters a recycling pathway and avoids lysosomal degradation; this process allows apicalbasal transcytosis of bound peptides. This mechanism is facilitated by Tgase2 and might be involved in the pathogenesis of celiac disease.
LanguageEnglish
Pages698–707
Number of pages10
JournalGastroenterology
Volume143
Issue number3
DOIs
Publication statusPublished - 1 Sep 2012

Fingerprint

Gliadin
Secretory Immunoglobulin A
Permeability
Epithelial Cells
Caco-2 Cells
Celiac Disease
Peptides
Transcytosis
Biopsy
Cell Line
Fluorescence Resonance Energy Transfer
Transferrin Receptors
Enterocytes
Endosomes
Recycling
Lysosomes
Immunoprecipitation
Confocal Microscopy
Abdomen
Immunoglobulin A

Keywords

  • intestinal transport
  • epithelial transcytosis
  • IgA
  • transferrin receptor

Cite this

Lebreton, Corinne ; Ménard, Sandrine ; Abed, Juliette ; Moura, Ivan C. ; Coppo, Rosanna ; Dugave, Christophe ; Monteiro, Renato C. ; Fricot, Aurélie ; Traore, Meriem G. ; Griffin, Martin ; Cellier, Christophe ; Malamut, Georgia ; Cerf-Bensussan, Nadine ; Heyman, Martine. / Interactions among secretory immunoglobulin A, CD71, and transglutaminase-2 affect permeability of intestinal epithelial cells to gliadin peptides. In: Gastroenterology. 2012 ; Vol. 143, No. 3. pp. 698–707.
@article{aec8e613f18e43d19c6b6561fcfdefd9,
title = "Interactions among secretory immunoglobulin A, CD71, and transglutaminase-2 affect permeability of intestinal epithelial cells to gliadin peptides",
abstract = "BACKGROUND & AIMS: The transferrin receptor (CD71) is up-regulated in duodenal biopsy samples from patients with active celiac disease and promotes retrotransport of secretory immunolglobulin A (SIgA)-gliadin complexes. We studied intestinal epithelial cell lines that overexpress CD71 to determine how interactions between SIgA and CD71 promote transepithelial transport of gliadin peptides. METHODS: We analyzed duodenal biopsy specimens from 8 adults and 1 child with active celiac disease. Caco-2 and HT29-19A epithelial cell lines were transfected with fluorescence-labeled small interfering RNAs against CD71. Interactions among IgA, CD71, and transglutaminase 2 (Tgase2) were analyzed by flow cytometry, immunoprecipitation, and confocal microscopy. Transcytosis of SIgACD71 complexes and intestinal permeability to the gliadin 3H-p3149 peptide were analyzed in polarized monolayers of Caco-2 cells. RESULTS: Using fluorescence resonance energy transfer and in situ proximity ligation assays, we observed physical interactions between SIgA and CD71 or CD71 and Tgase2 at the apical surface of enterocytes in biopsy samples and monolayers of Caco-2 cells. CD71 and Tgase2 were co-precipitated with SIgA, bound to the surface of Caco-2 cells. SIgACD71 complexes were internalized and localized in early endosomes and recycling compartments but not in lysosomes. In the presence of celiac IgA or SIgA against p3149, transport of intact 3H-p3149 increased significantly across Caco-2 monolayers; this transport was inhibited by soluble CD71 or Tgase2 inhibitors. CONCLUSIONS: Upon binding to apical CD71, SIgA (with or without gliadin peptides) enters a recycling pathway and avoids lysosomal degradation; this process allows apicalbasal transcytosis of bound peptides. This mechanism is facilitated by Tgase2 and might be involved in the pathogenesis of celiac disease.",
keywords = "intestinal transport, epithelial transcytosis, IgA, transferrin receptor",
author = "Corinne Lebreton and Sandrine M{\'e}nard and Juliette Abed and Moura, {Ivan C.} and Rosanna Coppo and Christophe Dugave and Monteiro, {Renato C.} and Aur{\'e}lie Fricot and Traore, {Meriem G.} and Martin Griffin and Christophe Cellier and Georgia Malamut and Nadine Cerf-Bensussan and Martine Heyman",
year = "2012",
month = "9",
day = "1",
doi = "10.1053/j.gastro.2012.05.051",
language = "English",
volume = "143",
pages = "698–707",
journal = "Gastroenterology",
issn = "0016-5085",
publisher = "W.B. Saunders Ltd",
number = "3",

}

Lebreton, C, Ménard, S, Abed, J, Moura, IC, Coppo, R, Dugave, C, Monteiro, RC, Fricot, A, Traore, MG, Griffin, M, Cellier, C, Malamut, G, Cerf-Bensussan, N & Heyman, M 2012, 'Interactions among secretory immunoglobulin A, CD71, and transglutaminase-2 affect permeability of intestinal epithelial cells to gliadin peptides' Gastroenterology, vol. 143, no. 3, pp. 698–707. https://doi.org/10.1053/j.gastro.2012.05.051

Interactions among secretory immunoglobulin A, CD71, and transglutaminase-2 affect permeability of intestinal epithelial cells to gliadin peptides. / Lebreton, Corinne; Ménard, Sandrine; Abed, Juliette; Moura, Ivan C.; Coppo, Rosanna; Dugave, Christophe; Monteiro, Renato C.; Fricot, Aurélie; Traore, Meriem G.; Griffin, Martin; Cellier, Christophe; Malamut, Georgia; Cerf-Bensussan, Nadine; Heyman, Martine.

In: Gastroenterology, Vol. 143, No. 3, 01.09.2012, p. 698–707.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Interactions among secretory immunoglobulin A, CD71, and transglutaminase-2 affect permeability of intestinal epithelial cells to gliadin peptides

AU - Lebreton, Corinne

AU - Ménard, Sandrine

AU - Abed, Juliette

AU - Moura, Ivan C.

AU - Coppo, Rosanna

AU - Dugave, Christophe

AU - Monteiro, Renato C.

AU - Fricot, Aurélie

AU - Traore, Meriem G.

AU - Griffin, Martin

AU - Cellier, Christophe

AU - Malamut, Georgia

AU - Cerf-Bensussan, Nadine

AU - Heyman, Martine

PY - 2012/9/1

Y1 - 2012/9/1

N2 - BACKGROUND & AIMS: The transferrin receptor (CD71) is up-regulated in duodenal biopsy samples from patients with active celiac disease and promotes retrotransport of secretory immunolglobulin A (SIgA)-gliadin complexes. We studied intestinal epithelial cell lines that overexpress CD71 to determine how interactions between SIgA and CD71 promote transepithelial transport of gliadin peptides. METHODS: We analyzed duodenal biopsy specimens from 8 adults and 1 child with active celiac disease. Caco-2 and HT29-19A epithelial cell lines were transfected with fluorescence-labeled small interfering RNAs against CD71. Interactions among IgA, CD71, and transglutaminase 2 (Tgase2) were analyzed by flow cytometry, immunoprecipitation, and confocal microscopy. Transcytosis of SIgACD71 complexes and intestinal permeability to the gliadin 3H-p3149 peptide were analyzed in polarized monolayers of Caco-2 cells. RESULTS: Using fluorescence resonance energy transfer and in situ proximity ligation assays, we observed physical interactions between SIgA and CD71 or CD71 and Tgase2 at the apical surface of enterocytes in biopsy samples and monolayers of Caco-2 cells. CD71 and Tgase2 were co-precipitated with SIgA, bound to the surface of Caco-2 cells. SIgACD71 complexes were internalized and localized in early endosomes and recycling compartments but not in lysosomes. In the presence of celiac IgA or SIgA against p3149, transport of intact 3H-p3149 increased significantly across Caco-2 monolayers; this transport was inhibited by soluble CD71 or Tgase2 inhibitors. CONCLUSIONS: Upon binding to apical CD71, SIgA (with or without gliadin peptides) enters a recycling pathway and avoids lysosomal degradation; this process allows apicalbasal transcytosis of bound peptides. This mechanism is facilitated by Tgase2 and might be involved in the pathogenesis of celiac disease.

AB - BACKGROUND & AIMS: The transferrin receptor (CD71) is up-regulated in duodenal biopsy samples from patients with active celiac disease and promotes retrotransport of secretory immunolglobulin A (SIgA)-gliadin complexes. We studied intestinal epithelial cell lines that overexpress CD71 to determine how interactions between SIgA and CD71 promote transepithelial transport of gliadin peptides. METHODS: We analyzed duodenal biopsy specimens from 8 adults and 1 child with active celiac disease. Caco-2 and HT29-19A epithelial cell lines were transfected with fluorescence-labeled small interfering RNAs against CD71. Interactions among IgA, CD71, and transglutaminase 2 (Tgase2) were analyzed by flow cytometry, immunoprecipitation, and confocal microscopy. Transcytosis of SIgACD71 complexes and intestinal permeability to the gliadin 3H-p3149 peptide were analyzed in polarized monolayers of Caco-2 cells. RESULTS: Using fluorescence resonance energy transfer and in situ proximity ligation assays, we observed physical interactions between SIgA and CD71 or CD71 and Tgase2 at the apical surface of enterocytes in biopsy samples and monolayers of Caco-2 cells. CD71 and Tgase2 were co-precipitated with SIgA, bound to the surface of Caco-2 cells. SIgACD71 complexes were internalized and localized in early endosomes and recycling compartments but not in lysosomes. In the presence of celiac IgA or SIgA against p3149, transport of intact 3H-p3149 increased significantly across Caco-2 monolayers; this transport was inhibited by soluble CD71 or Tgase2 inhibitors. CONCLUSIONS: Upon binding to apical CD71, SIgA (with or without gliadin peptides) enters a recycling pathway and avoids lysosomal degradation; this process allows apicalbasal transcytosis of bound peptides. This mechanism is facilitated by Tgase2 and might be involved in the pathogenesis of celiac disease.

KW - intestinal transport

KW - epithelial transcytosis

KW - IgA

KW - transferrin receptor

UR - http://www.scopus.com/inward/record.url?scp=84865462532&partnerID=8YFLogxK

U2 - 10.1053/j.gastro.2012.05.051

DO - 10.1053/j.gastro.2012.05.051

M3 - Article

VL - 143

SP - 698

EP - 707

JO - Gastroenterology

T2 - Gastroenterology

JF - Gastroenterology

SN - 0016-5085

IS - 3

ER -