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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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Density of various leukocyte subsets remains unchanged in duodenal mucosa of gluten-sensitive control subjects after short-term gluten challenge.Density of CD14+CD11c+ dendritic cells (DCs) per mm2 (A) and CD103+CD11c+ DCs per mm2 (B) in the lamina propria (LP); CD3+ intraepithelial lymphocytes (IELs) per 100 epithelial cells (C); neutrophils per mm2 (D) and eosinophils per mm2 (E) in the LP in sections of duodenal mucosa from gluten-sensitive control subjects 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-g006: Density of various leukocyte subsets remains unchanged in duodenal mucosa of gluten-sensitive control subjects after short-term gluten challenge.Density of CD14+CD11c+ dendritic cells (DCs) per mm2 (A) and CD103+CD11c+ DCs per mm2 (B) in the lamina propria (LP); CD3+ intraepithelial lymphocytes (IELs) per 100 epithelial cells (C); neutrophils per mm2 (D) and eosinophils per mm2 (E) in the LP in sections of duodenal mucosa from gluten-sensitive control subjects on gluten-free diet before and after a three-day gluten challenge. Paired data are connected by lines. ns = not significant.

Mentions: Next we wanted to examine whether the observed changes might represent an innate response to gluten independently of CD. To this end, we examined biopsy samples from gluten-sensitive control subjects on GFD who were challenged with gluten as described above. The gluten-sensitive controls were HLA-DQ2+ subjects without confirmed CD diagnosis, but with gluten-induced symptoms that subjectively improved on a GFD. As recently reported, no histopathological changes according to Marsh classification or tetramer-positive CD4+ T cells in peripheral blood were observed in this control group, although these patients experienced symptoms during the three-day gluten challenge [6]. Interestingly, as opposed to CD patients, no significant changes in the density of CD14+CD11c+ DCs, CD103+ DCs, neutrophils, eosinophils or CD3+ IELs were found after challenge (Figure 6). This finding indicates that the rapid recruitment of CD14+CD11c+ DCs and neutrophils, as well as the decrease of mucosal CD103+ DCs in response to gluten challenge are specific for CD.


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)

Density of various leukocyte subsets remains unchanged in duodenal mucosa of gluten-sensitive control subjects after short-term gluten challenge.Density of CD14+CD11c+ dendritic cells (DCs) per mm2 (A) and CD103+CD11c+ DCs per mm2 (B) in the lamina propria (LP); CD3+ intraepithelial lymphocytes (IELs) per 100 epithelial cells (C); neutrophils per mm2 (D) and eosinophils per mm2 (E) in the LP in sections of duodenal mucosa from gluten-sensitive control subjects 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-g006: Density of various leukocyte subsets remains unchanged in duodenal mucosa of gluten-sensitive control subjects after short-term gluten challenge.Density of CD14+CD11c+ dendritic cells (DCs) per mm2 (A) and CD103+CD11c+ DCs per mm2 (B) in the lamina propria (LP); CD3+ intraepithelial lymphocytes (IELs) per 100 epithelial cells (C); neutrophils per mm2 (D) and eosinophils per mm2 (E) in the LP in sections of duodenal mucosa from gluten-sensitive control subjects on gluten-free diet before and after a three-day gluten challenge. Paired data are connected by lines. ns = not significant.
Mentions: Next we wanted to examine whether the observed changes might represent an innate response to gluten independently of CD. To this end, we examined biopsy samples from gluten-sensitive control subjects on GFD who were challenged with gluten as described above. The gluten-sensitive controls were HLA-DQ2+ subjects without confirmed CD diagnosis, but with gluten-induced symptoms that subjectively improved on a GFD. As recently reported, no histopathological changes according to Marsh classification or tetramer-positive CD4+ T cells in peripheral blood were observed in this control group, although these patients experienced symptoms during the three-day gluten challenge [6]. Interestingly, as opposed to CD patients, no significant changes in the density of CD14+CD11c+ DCs, CD103+ DCs, neutrophils, eosinophils or CD3+ IELs were found after challenge (Figure 6). This finding indicates that the rapid recruitment of CD14+CD11c+ DCs and neutrophils, as well as the decrease of mucosal CD103+ DCs in response to gluten challenge are specific for CD.

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