Basic–alimentary tractReduced Chemokine Receptor 9 on Intraepithelial Lymphocytes in Celiac Disease Suggests Persistent Epithelial Activation
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Patients and Sampling
During diagnostic or follow-up gastroduodenoscopy, multiple duodenal biopsy specimens (n = 4–6) and concomitant blood samples were obtained from consecutively recruited patients with treated (n = 7; age range, 22–70 years) and untreated (n = 7; age range, 29–62 years) celiac disease as well as from non–celiac disease controls with a histologically normal mucosa (n = 6; age range, 28–69 years) (Table 1). Untreated patients had clinical symptoms and/or signs suggestive of celiac disease and
CCR9 Is Persistently Down-regulated on Intraepithelial T Cells in Celiac Disease
The dot plots in Figure 1 based on flow-cytometric analysis of isolated duodenal lymphocytes show the frequency of CCR9+ cells among CD3+ (Figure 1A–F) and CD8+ (Figure 1G–L) cells dispersed from the intestinal epithelium (Figure 1A–C and Figure 1G–I) or lamina propria (Figure 1D–F and Figure 1J–L) of a healthy control subject (no. 6; Figure 1A, D, G, and J) vs a treated (no. 7; Figure 1B, E, H, and K) or untreated (no. 19; Figure 1C, F, I, and L) patient with celiac disease. The number of CCR9+
Discussion
Circumstantial evidence suggests that some mucosal immune activation remains in celiac disease after clinically successful treatment with a GFD.13, 14 Because CCR9 is considered to be a small intestinal homing receptor apparently reflecting the cellular activation state, we analyzed epithelial and lamina propria T cells from treated and untreated patients with celiac disease for the expression of this chemokine receptor. In untreated patients, the frequency of duodenal CCR9+ T cells was
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2021, Journal of Translational AutoimmunityCitation Excerpt :Firstly, CCR9-positive dendritic cells play an essential role in maintaining gut homeostasis and tolerance by regulating the phenotype and function of both innate and adaptive immune cells [5]. Secondly, there is data to suggest that the number of CCR9-positive type 2 conventional dendritic cells is increased in circulation in untreated celiac disease [6] while the number of CCR9-expressing T cells is diminished in the small intestines of patients [7]. Thirdly, a clinical trial to test the efficacy of an oral CCR9 inhibitor as an alternative form of treatment for celiac disease has been performed but not yet published [8].
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2016, Molecular and Cellular NeuroscienceTherapeutic approaches for celiac disease
2015, Best Practice and Research: Clinical GastroenterologyCitation Excerpt :Lymphocyte homing to the gastrointestinal mucosa is aided by the chemokine receptor CCR9 and integrin α4β7 in a process mediated by their chemokine ligands CCL25 and MADCAM1, respectively [104]. Celiac patients have elevated CCR9-expressing peripheral blood T cells and MADCAM1 augmentation in the duodenum, suggesting targeting either of these homing mechanisms could be used to treat celiac patients [105,106]. CCX282-B (GSK1605786A) is a selective, orally bioavailable antagonist of human CCR9 that is undergoing clinical trials in Crohn's disease and celiac disease [107].
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Supported by the Norwegian Foundation for Health and Rehabilitation through the Norwegian Celiac Society, the University of Oslo, the Research Council of Norway, and the Norwegian Cancer Society.
The authors have no conflict of interest to disclose.
- 1
M.R.K.’s present affiliation is Dynal Bead Based Separation, Cell Separation and Expansion, Invitrogen Corp, Oslo, Norway.
- 2
M.R.K. and I.N.F. contributed equally to this work.