The role of CXCR3 and its ligands CXCL10 and CXCL11 in the pathogenesis of celiac disease

Abstract

The chemokine receptor CXCR3 and its ligands CXCL10 and CXCL11 have been suggested to give rise to the most relevant chemokine axis able to facilitate the entrance of immune cells into inflamed tissues and be activated in different inflammatory disorders, such as celiac disease (CD). The aim of this study was to investigate the expression level of CXCR3 , CXCL10 , and CXCL11 genes in celiac patients compared to healthy controls. Both cohorts have been recruited from the Iranian population. In this case–control study, biopsy specimens were collected from 71 celiac patients (60.5% female) and 90 control subjects (57% female) during 2016. Total RNA was extracted and mRNA expression levels of CXCR3 , CXCL10 , and CXCL11 genes were investigated by SYBR green qPCR. Based on qPCR and relative quantification method, the mRNA expression levels of CXCR3 , CXCL10, and CXCL11 were significantly higher in duodenal biopsies of celiac patients compared to healthy controls in the study population ( P = .038, P = .021, and P = .012 respectively). The result of this study showed that CXCR3/CXCL10 / CXCL11 signaling axis is overexpressed in the small intestinal mucosa of CD patients compared to controls. This finding might explain the specific enrollment of the main cell populations that infiltrate the epithelium.

New Insights into Non-Dietary Treatment in Celiac Disease: Emerging Therapeutic Options

“…Inhibition of transglutaminase (ZED 1227) [76] Blocker of HLA DQ binding to T-cells [77] NK lymphocyte activation blocker: NKG2D receptor antagonists [78] Lymphocyte recruitment blocker Anti-α4 integrin (natalizumab) [79] Anti…”

“…Among T-cell-targeted therapies aimed at blocking lymphocyte recruitment, natalizumab is an anti-α4 used in Crohn’s disease and could be useful in CD, although its side effects are very high [ 79 , 137 ]. Vedolizumab is scheduled to start phase II studies that block α4β7 integrin [ 138 ].…”

“…Vedolizumab is scheduled to start phase II studies that block α4β7 integrin [ 138 ]. In addition, chemokine receptor inhibitors such as CXCR3 and its specific ligands CXCL10 and CXCL11 have also been studied [ 79 ]. These molecules are among the main determinants in the recruitment of immune cells to the intestinal lamina propria and are involved in the uptake of lymphocytes in the presence of gliadin peptides.…”

From celiac disease to coccidia infection and vice‐versa: The polyQ peptide CXCR3‐interaction axis

“…And as observed in the model of Eimeria falciformis, [42] the expression of the mRNA of CxCR3, CXCL10, and CXCL11 are significantly higher in duodenal biopsies of active CeD patients than in healthy controls. [90] The only treatment for Coccidia infections is based on coccidiostat and coccidiocidal drugs. [91] In chicken, live coccidian vaccines were also employed; however, their usage is more restricted due to drug resistance and high production cost.…”

Novel targets for drug discovery in celiac disease

“…One of the approaches is also to introduce enzymes which could break or digest proline and glutamine bond in the immunogenic peptides. [678] ALV003 is an enzyme supplement, the mixture of two recombinant gluten-specific proteases and is in Phase 2b clinical trial as an adjunct therapy with a GFD [Table 1]. [10]…”