INSERM (INSTITUT NATIONAL DE LA SANTÉ ET DE LA RECHERCHE MÉDICALE);UNIVERSITÉ DE RENNES 1;ENIOS APPLICATIONS PRIVATE LIMITED COMPANY;UNIVERSITÉ PARIS DIDEROT - PARIS 7
The mucosa is an integrated network of tissues, cells and effector molecules that protect the host from environmental insults and infections. Dysregulation of immunity at mucosal surfaces is thought to lead to mucosal inflammatory diseases such as those affecting the gastrointestinal system (Crohn's disease, ulcerative colitis and irritable bowel syndrome) and respiratory system (asthma, allergy and chronic obstructive pulmonary disorder). Anterior Gradient 2 (AGR2) is a dimeric Protein Disulfide Isomerase (PDI) family member involved in the regulation of protein quality control in the Endoplasmic Reticulum (ER). Its deletion in the mouse intestine increases tissue inflammation and promotes the development of inflammatory bowel disease (IBD). Now the inventors demonstrate that modulation of AGR2 dimer formation yields pro-inflammatory phenotypes notably though the secretion of AGR2 (eAGR2) that promotes monocyte attraction. The inventors show that in IBD and specifically in Crohn's disease, the levels of AGR2 dimerization modulators are selectively deregulated, and this correlates with severity of disease. The inventors thus demonstrate that AGR2 represent systemic alarm signals for pro-inflammatory responses in mucosa. Accordingly, the present invention relates to a method of treating a mucosal inflammatory disease in a subject in need thereof comprising administering to the subject a therapeutically effective amount of an agent which neutralizes the pro-inflammatory activity of eAGR2.La présente invention se rapporte aux muqueuses en tant que réseau intégré de tissus, de cellules et de molécules effectrices qui protègent l'hôte contre les agressions environnementales et les infections. La dysrégulation de l'immunité au niveau des surfaces de muqueuses est censée conduire à des maladies inflammatoires des muqueuses telles que celles affectant le système gastro-intestinal (maladie de Crohn, colite ulcéreuse et syndrome du côlon irritable) et le système respiratoire
