The modulation of macrophage subsets in celiac disease pathogenesis

Abstract

Background So far, limited studies have focused on the role of Macrophages (MQs) in the development or progression of celiac disease (CD). Researchers believe that increasing knowledge about the function of MQs in inflammatory disorders plays a critical role in finding a new treatment for these kinds of diseases. Main body CD is a permanent autoimmune intestinal disorder triggered by gluten exposure in predisposed individuals. This disorder happens due to the loss of intestinal epithelial barrier integrity characterized by dysregulated innate and adaptive immune responses. MQs are known as key players of the innate immune system that link innate and adaptive immunity. MQs of human intestinal lamina propria participate in maintaining tissue homeostasis, and also intestinal inflammation development. Previous studies suggested that gliadin triggers a proinflammatory phenotype (M1 MQ) in human primary MQs. Moreover, M2‐related immunosuppressive mediators are also present in CD. In fact, CD patients present an impaired transition from pro‐inflammatory to anti‐inflammatory responses due to inappropriate responses to gliadin peptides. Conclusion The M1/M2 MQs polarization balancing regulators can be considered novel therapeutic targets for celiac disease.

CB2 Receptor as Emerging Anti-Inflammatory Target in Duchenne Muscular Dystrophy

“…The two prototypical macrophage phenotypes are M1, or classically activated macrophages with pro-inflammatory function, and M2, or alternatively activated macrophages with anti-inflammatory properties. They are generally balanced, but the ratio of M1/M2 is in favor of M1 subtypes in inflammatory and immune disease [ 17 , 18 , 48 , 49 ]. In the same manner, the switch of their phenotype towards the M2 one, namely, a reduction of the M1/M2 ratio, could apport benefits in different kind of diseases [ 17 , 18 ].…”

Intestinal mRNA expression analysis of polarity‐related genes identified the discriminatory ability of CRB3 as a diagnostic marker for celiac disease

“…The pathogenesis of CD involves inflammation and immune dysregulation, which contribute significantly to the development of the disease. A key factor in CD pathogenesis is the loss of integrity of the intestinal epithelial barrier, which is a result of inflammation 3,4 . Indeed, the impairment of the intestinal epithelial barrier leads to alterations in the positioning of both epithelial tight junctions (TJs) and adherens junctions (AJs).…”

“…A key factor in CD pathogenesis is the loss of integrity of the intestinal epithelial barrier, which is a result of inflammation. 3 , 4 Indeed, the impairment of the intestinal epithelial barrier leads to alterations in the positioning of both epithelial tight junctions (TJs) and adherens junctions (AJs). Consequently, there is an increased entrance of semi‐digested gluten peptides to the lamina propria, leading to the inflammatory responses.…”

Expression of Elafin and CD200 as Immune Checkpoint Molecules Involved in Celiac Disease

“…Galipeau et al [30] explored the role of Elafin in CD and its interaction with factors involved in its pathogenesis using human small intestinal tissue and in vitro gliadin deamidation assays. They observed a lower presence of the Elafin in patients with active CD, which reflects inflammation and damage to the small intestinal epithelium.…”

“…They observed a lower presence of the Elafin in patients with active CD, which reflects inflammation and damage to the small intestinal epithelium. Furthermore, they reported an improvement in inflammation and the restoration of the small intestinal epithelial barrier in a gluten-sensitive mouse model treated with Elafin, describing Elafin as a molecule capable of interacting with gliadin peptides and affecting TG-2, which is involved in their deamidation [30].…”