Circulating hematopoietic stem cells and putative intestinal stem cells in coeliac disease

Abstract

BackgroundThe intestinal stem cells (ISC) modulation and the role of circulating hematopoietic stem cells (HSC) in coeliac disease (CD) are poorly understood. Our aim was to investigate the longitudinal modifications in peripheral blood HSC traffic and putative ISC density induced by gluten-free diet (GFD) in CD.MethodsThirty-one CD patients and 7 controls were enrolled. Circulating CD133+ and CD34+ HSC were measured by flow cytometry, at enrolment and after 7 days and 1, 3, 6, 12, and 24 months of GFD. Endoscopy was performed at diagnosis and repeated at 6, 12, and 24 months following GFD. We used the Marsh-Oberhuber score to evaluate the histological severity of duodenal damage; immunohistochemistry was employed to measure the intraepithelial lymphoid infiltrate (IEL, CD3+ lymphoid cells) and the putative ISC compartment (CD133+ and Lgr5+ epithelial cells).ResultsAt enrolment, circulating HSCs were significantly increased in CD patients and they further augmented during the first week of GFD, but progressively decreased afterwards. CD patients presented with villous atrophy, abundant IEL and rare ISC residing at the crypt base. Upon GFD, IEL progressively decreased, while ISC density increased, peaking at 12 months. After 24 months of GFD, all patients were asymptomatic and their duodenal mucosa was macroscopically and histologically normal.ConclusionsIn active CD patients, the ISC niche is depleted and there is an increased traffic of circulating HSC versus non-coeliac subjects. GFD induces a precocious mobilization of circulating HSC, which is followed by the expansion of the local ISC compartment, leading to mucosal healing and clinical remission.

Human gut derived-organoids provide model to study gluten response and effects of microbiota-derived molecules in celiac disease

“…Histological features including crypt hyperplasia and blunting of the villi are the hallmark of active CD characterized by expansion of the immature-cell population and concurring reduction of the mature cells of the villus 31 . These pathological manifestations of the CD intestinal mucosa have been hypothesized to be the consequence of a faulty stem cell compartment that cannot compensate the tissue turnover and/or a consequence of increased epithelium apoptosis 32,33 .…”

Doublecortin‐like kinase 1‐positive enterocyte – a new cell type in human intestine

“…In this study, we wanted to characterize DCLK1‐positive cells in the normal human duodenal epithelium and in other parts of intestine. Additionally, to address potential stem cell‐related role of the DCLK1‐positive cells, we studied a series of patients with coeliac disease, where depletion of stem cells plays a role in pathogenesis .…”

Genome-Wide Transcriptomic Analysis of Intestinal Mucosa in Celiac Disease Patients on a Gluten-Free Diet and Postgluten Challenge

“…Differentiation of both absorptive and secretory epithelial cells has been shown to be affected in celiac disease. 28 , 29 When comparing our biopsy transcriptomic data to published data on single-cell RNA-Seq studies on the small intestinal epithelium, 30 we found that mature absorptive enterocyte lineage genes were almost unanimously downregulated in PGC patients. Interestingly, however, we found that genes for secretory cell signatures were upregulated during the gluten challenge ( Figure 9 A ), and most of these genes belong to the goblet cell signature.…”