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Rapid accumulation of CD14+CD11c+ dendritic cells in gut mucosa of celiac disease after in vivo gluten challenge.

Beitnes AC, Ráki M, Brottveit M, Lundin KE, Jahnsen FL, Sollid LM - PLoS ONE (2012)

Bottom Line: The density of neutrophils also increased in the challenged mucosa, but in most patients no architectural changes or increase of CD3(+) intraepithelial lymphocytes (IELs) were found.In control tissue no significant changes were observed.The expression of CCR2 and CD14 on the accumulating CD11c(+) DCs indicates that these cells are newly recruited monocytes.

View Article: PubMed Central - PubMed

Affiliation: Centre for Immune Regulation and Department of Immunology, Oslo University Hospital - Rikshospitalet, Oslo, Norway. Ann-Christin.Beitnes@rr-research.no

ABSTRACT

Background: Of antigen-presenting cells (APCs) expressing HLA-DQ molecules in the celiac disease (CD) lesion, CD11c(+) dendritic cells (DCs) co-expressing the monocyte marker CD14 are increased, whereas other DC subsets (CD1c(+) or CD103(+)) and CD163(+)CD11c(-) macrophages are all decreased. It is unclear whether these changes result from chronic inflammation or whether they represent early events in the gluten response. We have addressed this in a model of in vivo gluten challenge.

Methods: Treated HLA-DQ2(+) CD patients (n = 12) and HLA-DQ2(+) gluten-sensitive control subjects (n = 12) on a gluten-free diet (GFD) were orally challenged with gluten for three days. Duodenal biopsies obtained before and after gluten challenge were subjected to immunohistochemistry. Single cell digests of duodenal biopsies from healthy controls (n = 4), treated CD (n = 3) and untreated CD (n = 3) patients were analyzed by flow cytometry.

Results: In treated CD patients, the gluten challenge increased the density of CD14(+)CD11c(+) DCs, whereas the density of CD103(+)CD11c(+) DCs and CD163(+)CD11c(-) macrophages decreased, and the density of CD1c(+)CD11c(+) DCs remained unchanged. Most CD14(+)CD11c(+) DCs co-expressed CCR2. The density of neutrophils also increased in the challenged mucosa, but in most patients no architectural changes or increase of CD3(+) intraepithelial lymphocytes (IELs) were found. In control tissue no significant changes were observed.

Conclusions: Rapid accumulation of CD14(+)CD11c(+) DCs is specific to CD and precedes changes in mucosal architecture, indicating that this DC subset may be directly involved in the immunopathology of the disease. The expression of CCR2 and CD14 on the accumulating CD11c(+) DCs indicates that these cells are newly recruited monocytes.

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Neuthrophils are increased in duodenal mucosa of celiac disease patients after short-term gluten challenge.Density of CD3+ intraepithelial lymphocytes (IELs) per 100 epithelial cells (A); neutrophils per mm2 (B); and eosinophils per mm2 (C) in the lamina propria (LP) in sections of duodenal mucosa from celiac disease patients on gluten-free diet before and after a three-day gluten challenge. Paired data are connected by lines. ns = not significant.
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pone-0033556-g004: Neuthrophils are increased in duodenal mucosa of celiac disease patients after short-term gluten challenge.Density of CD3+ intraepithelial lymphocytes (IELs) per 100 epithelial cells (A); neutrophils per mm2 (B); and eosinophils per mm2 (C) in the lamina propria (LP) in sections of duodenal mucosa from celiac disease patients on gluten-free diet before and after a three-day gluten challenge. Paired data are connected by lines. ns = not significant.

Mentions: The histopathology of the CD lesion is characterized by villous blunting, crypt hyperplasia and increased numbers of IELs [3]. Next we wished to determine whether accumulation of CD14+CD11c+ DCs preceded typical features of an established celiac lesion. In the same biopsy material, Brottveit et al. recently showed that in most patients there were no significant changes in tissue architecture after a three-day gluten challenge [6]. Only four of twelve patients had changes according to Marsh classification. As increased numbers of CD3+ IELs is one of the first signs of CD [19], [20], we counted CD3+ IELs in all samples. Importantly, no difference in the number of CD3+ IELs was detected comparing tissue obtained before and after challenge (Figure 4A). Thus, the increase of CD14+CD11c+ DCs precedes the histopathological hallmarks of an active CD lesion.


Rapid accumulation of CD14+CD11c+ dendritic cells in gut mucosa of celiac disease after in vivo gluten challenge.

Beitnes AC, Ráki M, Brottveit M, Lundin KE, Jahnsen FL, Sollid LM - PLoS ONE (2012)

Neuthrophils are increased in duodenal mucosa of celiac disease patients after short-term gluten challenge.Density of CD3+ intraepithelial lymphocytes (IELs) per 100 epithelial cells (A); neutrophils per mm2 (B); and eosinophils per mm2 (C) in the lamina propria (LP) in sections of duodenal mucosa from celiac disease patients on gluten-free diet before and after a three-day gluten challenge. Paired data are connected by lines. ns = not significant.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3306402&req=5

pone-0033556-g004: Neuthrophils are increased in duodenal mucosa of celiac disease patients after short-term gluten challenge.Density of CD3+ intraepithelial lymphocytes (IELs) per 100 epithelial cells (A); neutrophils per mm2 (B); and eosinophils per mm2 (C) in the lamina propria (LP) in sections of duodenal mucosa from celiac disease patients on gluten-free diet before and after a three-day gluten challenge. Paired data are connected by lines. ns = not significant.
Mentions: The histopathology of the CD lesion is characterized by villous blunting, crypt hyperplasia and increased numbers of IELs [3]. Next we wished to determine whether accumulation of CD14+CD11c+ DCs preceded typical features of an established celiac lesion. In the same biopsy material, Brottveit et al. recently showed that in most patients there were no significant changes in tissue architecture after a three-day gluten challenge [6]. Only four of twelve patients had changes according to Marsh classification. As increased numbers of CD3+ IELs is one of the first signs of CD [19], [20], we counted CD3+ IELs in all samples. Importantly, no difference in the number of CD3+ IELs was detected comparing tissue obtained before and after challenge (Figure 4A). Thus, the increase of CD14+CD11c+ DCs precedes the histopathological hallmarks of an active CD lesion.

Bottom Line: The density of neutrophils also increased in the challenged mucosa, but in most patients no architectural changes or increase of CD3(+) intraepithelial lymphocytes (IELs) were found.In control tissue no significant changes were observed.The expression of CCR2 and CD14 on the accumulating CD11c(+) DCs indicates that these cells are newly recruited monocytes.

View Article: PubMed Central - PubMed

Affiliation: Centre for Immune Regulation and Department of Immunology, Oslo University Hospital - Rikshospitalet, Oslo, Norway. Ann-Christin.Beitnes@rr-research.no

ABSTRACT

Background: Of antigen-presenting cells (APCs) expressing HLA-DQ molecules in the celiac disease (CD) lesion, CD11c(+) dendritic cells (DCs) co-expressing the monocyte marker CD14 are increased, whereas other DC subsets (CD1c(+) or CD103(+)) and CD163(+)CD11c(-) macrophages are all decreased. It is unclear whether these changes result from chronic inflammation or whether they represent early events in the gluten response. We have addressed this in a model of in vivo gluten challenge.

Methods: Treated HLA-DQ2(+) CD patients (n = 12) and HLA-DQ2(+) gluten-sensitive control subjects (n = 12) on a gluten-free diet (GFD) were orally challenged with gluten for three days. Duodenal biopsies obtained before and after gluten challenge were subjected to immunohistochemistry. Single cell digests of duodenal biopsies from healthy controls (n = 4), treated CD (n = 3) and untreated CD (n = 3) patients were analyzed by flow cytometry.

Results: In treated CD patients, the gluten challenge increased the density of CD14(+)CD11c(+) DCs, whereas the density of CD103(+)CD11c(+) DCs and CD163(+)CD11c(-) macrophages decreased, and the density of CD1c(+)CD11c(+) DCs remained unchanged. Most CD14(+)CD11c(+) DCs co-expressed CCR2. The density of neutrophils also increased in the challenged mucosa, but in most patients no architectural changes or increase of CD3(+) intraepithelial lymphocytes (IELs) were found. In control tissue no significant changes were observed.

Conclusions: Rapid accumulation of CD14(+)CD11c(+) DCs is specific to CD and precedes changes in mucosal architecture, indicating that this DC subset may be directly involved in the immunopathology of the disease. The expression of CCR2 and CD14 on the accumulating CD11c(+) DCs indicates that these cells are newly recruited monocytes.

Show MeSH
Related in: MedlinePlus