Rapid Accumulation of CD14+CD11c+ Dendritic Cells in Gut Mucosa of Celiac Disease after in vivo Gluten Challenge

Abstract

BackgroundOf 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.MethodsTreated 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.ResultsIn 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.ConclusionsRapid 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.

Increased Expression of TLR4 and TLR7 but Not Prolactin mRNA by Peripheral Blood Monocytes in Active Celiac Disease

“…This is supported by the fact that it has been shown that elevated serum PRL levels in CD patients correlate with disease activity indicated by the presence of malnutrition and the degree of histological damage of the intestinal mucosa [10]. PBMs circulate in blood vessels and migrate to the site of inflammation in the duodenal mucosa [32]; their signaling affects the organism both at the local and the systemic levels. PBMs are known to express PRL and its receptor; the question, however, was whether monocyte-derived PRL plays any role in the pathogenesis of CD.…”

Increased production of interleukin-21, but not interleukin-17A, in the small intestine characterizes pediatric celiac disease

“…In CD, neutrophilic influx has been reported previously. 22 Whether IL-21-secreting neutrophils in the celiac lesion have a specific function in B-cell stimulation will need to be investigated. Using serial tissue sections of our pediatric CD patient cohort, we established that the number of IL-17-secreting cells did not increase with disease score and remained comparable with nondiseased control tissues.…”

Rheumatoid arthritis–celiac disease relationship: Joints get that gut feeling

“…tion in animal studies [80][81][82][83][84]. A comparable trend is seen in human 272 diabetes type 1 [85] and CD [86,87] but the effects are controversial in 273 non-celiac gluten sensitivity [88,89]. Most recently, gluten was found 274 to breach tight junction integrity, not only in CD and non-celiac gluten 275 sensitivity, but interestingly enough, also in normal controls [90].…”