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Mucosal dendritic cells in intestinal homeostasis and bacteria-related diseases

Objective

The bacterial microflora has always been regarded as beneficial for the host but recent studies have shown that this symbiosis has risks as well as benefits. Although active mechanisms allow tolerating the commensal flora, the physiological stress that is associated with the symbionts’ metabolism can exhaust the intestinal barrier resulting in serious effects on the health of the host. Protracted immune deregulations can lead to severe disorders including diabetes, cancer and inflammatory bowel disease (IBD). Several mechanisms and players are involved in the maintenance of intestinal immune homeostasis, including T regulatory cells and Immunoglobulin (Ig)-A. In this proposal we focus our attention on dendritic cells (DCs) for their ability to induce both tolerance and immunity by regulating B and T cell responses. We have recently shown that DC function is controlled by intestinal epithelial cell (EC) derived factors and in particular by Thymic stromal lymphopoietin (TSLP). EC-conditioned DCs acquire a ‘mucosal’ phenotype as they are prone to activate T regulatory cells and IgA responses. Three major issues related to the maintenance and disruption of intestinal immune homeostasis will be explored in this project: 1) What are the mediators and mechanisms that regulate the interaction between intestinal epithelial cells and dendritic cells? What is the function of TSLP? 2) Which are the sites and players for the activation of an IgA response to pathogenic and commensal bacteria? Can we visualize them in vivo? 3) Can prolonged infections or bacterial products promote intestinal tumour development? Are there different bacterial constituents acting as inducers or protectors of carcinogenesis? What is the role of Toll-like receptors?

Field of science

  • /medical and health sciences/basic medicine/physiology/homeostasis
  • /natural sciences/biological sciences/microbiology/bacteriology
  • /medical and health sciences/clinical medicine/gastroenterology/inflammatory bowel disease

Call for proposal

ERC-2007-StG
See other projects for this call

Funding Scheme

ERC-SG - ERC Starting Grant

Host institution

ISTITUTO EUROPEO DI ONCOLOGIA SRL
Address
Via Filodrammatici 10
20121 Milano
Italy
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
EU contribution
€ 1 195 680
Principal investigator
Maria Rescigno (Dr.)
Administrative Contact
Ilaria Foti (Ms.)

Beneficiaries (1)

ISTITUTO EUROPEO DI ONCOLOGIA SRL
Italy
EU contribution
€ 1 195 680
Address
Via Filodrammatici 10
20121 Milano
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Principal investigator
Maria Rescigno (Dr.)
Administrative Contact
Ilaria Foti (Ms.)