DOP08 Cellular and molecular interaction of MAIT in mucosal tissue and their role in inflammatory bowel disease
Bosáková, V.(1,2)*;Frič, J.(1,3);
(1)St. Anne's University Hospital Brno, International Clinical Research Center, Brno, Czech Republic;(2)Masaryk University- Faculty of Medicine, Department of Biology, Brno, Czech Republic;(3)Institute of Hematology and Blood Transfusion, Department of Modern Immunotherapy, Prague, Czech Republic;
Background
Inflammatory bowel disease (IBD) manifests as chronic inflammation of the gastrointestinal tract and is characterized by a deregulated immune response targeting the gut microflora. Mucosal-associated invariant T (MAIT) cells have been identified as a possible key player in IBD. Activated MAIT cells produce cytokines including IL-26, a newly discovered cytokine involved in the pathology of IBD. Interestingly, IL-26 is not expressed in mice and therefore its effect on the course of inflammation has not been yet fully investigated. Similarly, studies employing human cell cultures often provide limited results as they cannot fully mimic the complex three-dimensional structure of the intestinal tissue. A great hope is placed in the development of models of human diseases using organoids - 3D structures that better recapitulate the architecture and functionality of tissues.
Methods
Our laboratory recently described a model of intestinal inflammation based on human iPSCs-derived intestinal organoids (IOs). Taking advantage of this model, we investigate the influence of the cytokine IL-26 on the course of IBD. Moreover, we elucidate the influence of MAIT cells on the pathogenesis of IBD by studying their pathways of activation in vitro, and subsequently their interaction with inflamed tissues through the co-culture with IOs.
Results
After stimulation, IOs mimic the pro-inflammatory microenvironment and express various cytokines and chemokines. Moreover, IOs express MR1 which is recognised by the invariant TCR receptor of the MAIT cells. IOs express functional IL-26 receptor and respond to this cytokine.
MAIT cells isolated from human blood show production cytokines including IL-26 and effector molecules upon in vitro activation. Their response differs depending on the origin of the stimuli.
Conclusion
IOs form complex structures and immunocompetent environment allowing to study of intestinal inflammation. IOs consist of various cell types, but not immune cells. Taken together with MR1 and cytokines expression we show that IOs can activate MAIT cells, and they serve as a relevant model for in vitro study of their biology. Moreover, IOs respond to IL-26, so they also provide a relevant model to elucidate the role of this cytokine. We expect that this study will contribute to our understanding of the processes underlying the progression of IBD, and lead to the design of new therapeutic targets for the treatment of idiopathic intestinal inflammation.