Diverse Profiles of Toll-Like Receptors 2, 4, 7, and 9 mRNA in Peripheral Blood and Biopsy Specimens of Patients with Celiac Disease

Abstract

Background and Aims Both adaptive and innate immunity are involved in the development of celiac disease (CD). Altered Toll-like receptors (TLR) expression and activation may be partially responsible for the inflammation and subsequently crypt hyperplasia, but the main driver for inflammation is gliadin-reactive T-cells. Therefore, the aim of this study was to investigate the TLRs 2, 4, 7, and 9 gene expressions in both peripheral blood and intestinal mucosa of patients with celiac disease compared to healthy control (HC). Material and Methods Blood samples from 120 confirmed active CD patients and 120 age- and sex-matched healthy volunteers served as control group were collected during 2015-2016. Also, 20 biopsy specimens from the study group were randomly collected. Total RNA was isolated using a standard commercial kit. The mRNA expression of TLRs was quantified by relative qPCR with β2 microglobulin (β2m) as a reference gene. Results TLR4 (P = 0.01) and TLR9 (P = 0.02) mRNA were significantly elevated in blood samples from CD patients compared to the healthy controls. Moreover, TLR2 (P = 0.03) and TLR4 (P = 0.0003) expression level was increased in CD biopsy specimens compared to controls, whereas expression of TLR9 mRNA was significantly decreased in CD patients. There was no significant difference in the expression of TLR7 in biopsy and blood specimens. Conclusions The alteration of TLR4 and TLR9 expression in the blood and biopsy samples of patients with CD supports the critical role of the innate immune system in the pathogenesis of this disease. Upregulation of TLR4 and TLR9 suggests the contribution of gut microbiota or dysregulation of the immune response to commensal flora in small bowel mucosa in celiac patients.

The Revival of the Battle between David and Goliath in the Enteric Viruses and Microbiota Struggle: Potential Implication for Celiac Disease

“…The pro-inflammatory interferon γ is involved in mucosal damage, dictates epigenetic immune outcomes and is sensitive to gluten challenge in CD patients [82,83,84,85,86]. Interestingly, mucosal TLR9 gene expression is increased in CD, suggesting the contribution of the microbiota or dysregulation of the immune response to the small bowel flora in the CD intestine [87,88]. The bacteriophage’s involvement in intestinal inflammation in colitis can potentially take place in the CD gut mucosal compartment.…”

Inflammation in acute coronary syndrome: Expression of TLR2 mRNA is increased in platelets of patients with ACS

“…Opposed regulation of TLR2 compared to TLR9 and TLR4 mRNA expression patterns has been described before. [70, 71] Apart from the high sequence homology between TLR2 and TLR4 they seem to react to different stimuli and elicit individual stimuli. Our data confirms this hypothesis.…”

The Roles of TRAF3 in Immune Responses

“…Recently, Ghasiyari et al published a large case-control study (120 CD patients and 120 controls) where mRNA expression of several TLRs (TLR2, TLR4, TLR7, and TLR9) was assessed in the intestinal mucosa for 20 randomly selected samples only. Regarding duodenal mucosa specimens, TLR2 and TLR4 mRNA expression was increased in CD patients compared to controls, whereas TLR9 mRNA expression was significantly decreased in CD patients; no significant difference in the expression of TLR7 mRNA was observed between the study groups [ 107 ]. On the other hand, celiac diseases are related to HLA-related genetic factors.…”