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eSymposia | Tissue Plasticity: Preservation and Alteration of Cellular Identity


The IL33/ST2 axis in Celiac Disease


Oct 5, 2020 12:00am ‐ Oct 5, 2020 12:00am

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The IL33/ST2 axis in Celiac Disease Federico Perez1, Carolina Ruera1, Emanuel Miculan1, Paula Carasi1, Karen Dubois-Camacho2, Laura Garbi3, Luciana Guzman3, Marcela A. Hermoso2, Fernando Chirdo1 1Instituto de Estudios Inmunológicos y Fisiopatológicos UNLP-CONICET, Argentina. 2Innate Immunity Laboratory, Immunology Program, Biomedical Sciences Institute, Universidad de Chile, Chile. 3Gastroenterology Unit of San Martin Hospital of La Plata and Sor Maria Ludovica, Children Hospital of La Plata. Argentina. IL-33 is cytokine able to promote regulatory T cells, reparation processes and type 2 immune responses in the gut. These functions can be inhibited by the presence of IFN???? and IL-23. Furthermore, IL-33 functions are regulated by a soluble form of its cellular receptor (ST2L), named sST2 (Molofsky et al. 2015). Celiac Disease (CD) is characterized by an immune response dominated by IFN????+ Th1 cells responsive to gluten, and enterocyte death by cytotoxic CD8+ T cells (Meresse et al. 2006). In this context, we have found that IL-33 and sST2 are increased in sera of CD patients. Also, CD8+ T cells are differentially increased in active CD patients. Additionally, CD patients have an increase in the ST2L as well as, in sST2 in CD duodenum. Thus, it is possible that IL-33 could target ST2L+ cells. Western blot analysis showed an increase in IL-33 mature fragments of about 18-20 kDa in protein extracts of duodenal samples of CD patients. These fragments are thought to be produced by granulocytes derived enzymes in the extracellular medium, and have much greater bioactivity on target cells (Lefrançais et al. 2012; 2014). Inflammatory cell death is considered to be one of the main sources of free IL-33 in inflamed tissues. Accordingly, we have found that Cleaved Caspase 1 and active IL1β, as markers of pyroptosis, are increased in CD patients. Therefore, IL-33 may act as a pro-cytotoxic alarmin released by pyroptotic cells in CD patients. In turn free IL-33 may boost programmed cell death mechanisms on stressed cells by targeting Cytotoxic ST2L+ CD8+T cells. Also, we considered that its wound-healing and regulatory properties may be inhibited by IFN???? and IL-23, which are released in response to gluten (Nilsen et al. 1998; Harris, et al. 2008). This work was funded by grant PICT 2017 0880 from the Agencia Nacional de Promoción Científica y Tecnológica from Ministerio de Ciencia, Argentine.

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