Title : Co-inhibitory immune checkpoints in celiac disease
Abstract:
Immune checkpoints are regulators of key processes in the immune system. These molecules represent the modulators of the signalling pathway responsible for immunological tolerance, a concept that prevents the destruction of "auto" cells by the immune system. Specifically, immune checkpoint inhibitors are currently the new targets due to their therapeutic potential. We have provided the first evidence of high PD-L1 expression levels in celiac patients on the surface of intestinal epithelial cells and lamina propria cells. Also, we have found that the enzyme IDO is highly expressed in intestinal biopsies from patients with celiac disease, that result in elevated levels of kynurenine in the serum of these patients. The aim of this study was show that signalling by co-inhibitory PD-L1, CD200 and by immunosuppressive IDO was altered in celiac disease patients Therefore we have analysed the CD200/CD200R pathway expression with important clinical and laboratory parameters in celiac disease. Many researches have demonstrated the importance of CD200 in controlling autoimmunity and inflammation, between others diseases associated with increased immune system activity. CD200/CD200R pathway provide immunomodulatory effects to induce immune tolerance and regulate cytokines release. CD200/C200R-signaling pathway has not been fully investigated in celiac disease. We have found abnormalities in the expression of elements of the CD200/CD200R pathway in celiac disease patients in the form of overexpression of the ligand and down-regulation of the receptor when compared to health controls. We demonstrated a significantly higher level of soluble CD200 in the serum of celiac disease patients as compared to healthy controls. CD200s protein expression was positively correlated with PD-L1 and IDO expression. Co-inhibitory immune checkpoints expression may reflect a compensating mechanism among them, when other immunoregulatory pathways such as direct PD-1/PD-L1 and CD200R/CD200 mediated inhibition fails.
Audience Take Away:
1) The immune checkpoint inhibitors are altered in celiac disease and can be new targets due to their therapeutic potential..
2) Dietary gluten peptides can modulate processes required for cell homeostasis through the splicing of pre-mRNAs encoding these regulatory proteins
3) Alterations in the alternative splicing process could lead to the production of deficient proteins that contribute to the development of celiac disease
