Unravelling innate and adaptive immune responses to gluten in coeliac disease
Principal investigator: Professor Sonia Quaratino
Institution: University of Southampton
Research classification: Aetiology
Project completion: 2010
Grant awarded: £175K
This project was aimed to define how the activation of the innate immune system is induced , how it influences the adaptive immune response, thus further clarifying the pathogenesis.
The main focus of this research was to determine the mechanisms involved in the inflammation underlying coeliac disease. To gain an understanding as to why some toxic gliadin peptides,in particular p31-43, can initiate an immune response and lead to an upregulation of tissue transglutaminase (TG2) in the coeliac intestine.
Laboratory methods were used to investigate the signalling pathways in cells that lead to activation and persistent inflammation controlled by TG2.
Gaining a greater understanding of the mechanisms involved in the inflammation in coeliac disease is one of the necessary steps that must be taken to progress towards developing alternative treatments.
Maiuri L, Luciani A, Villella VR, et al. 2010 Lysosomal accumulation of gliadin p31-43 peptide induces oxidative stress and tissue transglutaminase-mediated PPARgamma down regulation in intestinal epithelial cells and coeliac mucosa. Gut. 2010 Mar;59(3):311-9
Luciani A, Villella VR, Vasaturo A, et al. 2009 SUMOoylation of tissue transglutaminase as link between oxidative stress and inflammation. J Immunol. Aug 15;183(4):2775-84
Maiuri L, Ciacci C, Ricciarddelli I et al 2005 Unexpected role of surface transglutaminase type II in celiac disease. Gastroenterology 129 (5) 1400-13.