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Immune mechanisms that control the homeostasis of the gut and that are deregulated in intestinal pathologies cancer

Objective

This project stems from an ERC STG grant that I received in 2007 (DENDROworld) in which we analyzed several aspects of the homeostasis of the gut and how defects in controlling this process could result in different pathologies, including inflammatory bowel disease (IBD) and cancer. In the present project, we will continue working on the immune homeostasis of the gut and we will focus on fundamental questions in mucosal immunity.
Three important and novel questions will be addressed in this project. The first aims at understanding how the gut microbiota is restrained from reaching systemic sites and hence it is tolerated only locally. We think that we have identified a new barrier at mucosal sites that avoids systemic spreading of bacteria via the blood stream. This is a very selective barrier that resembles the blood brain barrier and occurs at the level of enteric endothelial cells. The second question is closely related and tries to identify the role of the microbiota in the establishment/maintenance of this barrier and to understand its role during infection with enteric pathogens or in other circumstances (like pregnancy, liver disease). Finally, we want to characterize the activity of an anti-inflammatory mediator that we have identified. This is a short isoform of the well-known cytokine called TSLP. We think that this isoform is the one involved in the homeostasis of the intestine as it is the only one produced by epithelial cells in health and is downregulated during chronic inflammation.
This project is divided into three major aims.
1. Analysis of a putative gut vascular barrier that resembles the blood brain barrier and of the mechanisms leading to its disruption
2. Analysis of the role of the microbiota in the formation and maintenance of the Gut vascular barrier (GVB).
3. Elucidation of the activity of TSLP short isoform.
This is a multidisciplinary project requiring expertise in mucosal immunology, microbiology, bioinformatics and endothelium.

Field of science

  • /medical and health sciences/basic medicine/pathology
  • /medical and health sciences/basic medicine/physiology/homeostasis
  • /medical and health sciences/basic medicine/immunology
  • /medical and health sciences/clinical medicine/oncology/cancer
  • /natural sciences/biological sciences/microbiology
  • /medical and health sciences/clinical medicine/gastroenterology/inflammatory bowel disease

Call for proposal

ERC-2013-CoG
See other projects for this call

Funding Scheme

ERC-CG - ERC Consolidator Grants

Host institution

UNIVERSITA DEGLI STUDI DI MILANO
Address
Via Festa Del Perdono 7
20122 Milano
Italy
Activity type
Higher or Secondary Education Establishments
EU contribution
€ 1 110 550
Principal investigator
Maria Rescigno (Dr.)
Administrative Contact
Gerardo D'errico (Dr.)

Beneficiaries (3)

UNIVERSITA DEGLI STUDI DI MILANO
Italy
EU contribution
€ 1 110 550
Address
Via Festa Del Perdono 7
20122 Milano
Activity type
Higher or Secondary Education Establishments
Principal investigator
Maria Rescigno (Dr.)
Administrative Contact
Gerardo D'errico (Dr.)
CONSIGLIO NAZIONALE DELLE RICERCHE
Italy
EU contribution
€ 108 000
Address
Piazzale Aldo Moro 7
00185 Roma
Activity type
Research Organisations
Administrative Contact
Marisa Mirizzi (Ms.)
ISTITUTO EUROPEO DI ONCOLOGIA SRL
Italy
EU contribution
€ 781 450
Address
Via Filodrammatici 10
20121 Milano
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Administrative Contact
Ilaria Foti (Ms.)