Co-inhibitory immune checkpoints in celiac disease

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

Biography:

Maria Isabel Torres Lopez is a Professor of Cell Biology at Jaen University School of Sciences (Spain). She received her PhD with a special award in 1994 from the University of Granada, Spain. She joined the Jaen University School of Sciences faculty as an assistant professor of cell biology from 1995 to 1999 and was appointed Professor of Cell Biology in 1999. Her lab research focuses on the field of inflammation and tolerance in two areas: (1) evaluating the immunotoxic ability of peptidic fragments derived from gluten in vitro, and (2) investigating the role of tolerance molecules in inflammatory bowel disease and celiac disease. In recent years, she has been conducting research on HLA-G and monitoring immunosuppression in heart transplantation. The relevance of tolerogenic molecules (HLA-G, IDO) in human physiological and pathological contexts has been the center of her intense investigation. She has published over 60 scientific papers, invited reviews, and book chapters. Currently, she serves on the Editorial Board of the World Journal of Gastroenterology, Trends in Applied Sciences Research, and the Journal of Tryptophan Research, and she is a member of national and international research public committees that evaluate research projects. She has presented invited talks at international and national meetings such as the International Conference of HLA-G, Congress of Immunology, and Congress of Pediatric Gastroenterology and Nutrition, among others. She has also been a visiting professor in the Developmental Gastroenterology Laboratory at Massachusetts, the Department of Cell Biology and Anatomy at the Medical University of South Carolina, and the Service de Recherches en Hemato-Immunologie at Hospital Saint-Louis, Paris.