7TREIMHO

7kDa TSLP as a novel type of anti-inflammatory agent to re-establish immune homeostasis

Coordinatore	ISTITUTO EUROPEO DI ONCOLOGIA SRL    more Spiacenti, non ci sono informazioni su questo coordinatore. Contattare Fabio per maggiori infomrazioni, grazie.
Nazionalità Coordinatore	Italy [IT]
Totale costo	163˙916 €
EC contributo	146˙917 €
Programma	FP7-IDEAS-ERC Specific programme: "Ideas" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013)
Code Call	ERC-2012-PoC
Funding Scheme	CSA-SA(POC)
Anno di inizio	2013
Periodo (anno-mese-giorno)	2013-07-01   -   2014-06-30

 Partecipanti

#	participant	country	role	EC contrib. [€]
1	IFOM FONDAZIONE ISTITUTO FIRC DI ONCOLOGIA MOLECOLARE  Organization address address: "Via Adamello, 16" city: MILAN postcode: 20139 contact info Titolo: Mr. Nome: Carlo Cognome: Raimondi Cominesi Email: send email Telefono: 3902570000000 Fax: 3902570000000	IT (MILAN)	beneficiary	19˙260.00
2	ISTITUTO EUROPEO DI ONCOLOGIA SRL  Organization address address: Via Filodrammatici 10 city: MILANO postcode: 20121 contact info Titolo: Ms. Nome: Ilaria Cognome: Foti Email: send email Telefono: 390257000000 Fax: 390257000000	IT (MILANO)	hostInstitution	127˙657.00

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 Obiettivo del progetto (Objective)

'Intestinal homeostasis is a complex event that relies on different interactions between the host and the commensal flora, also called microbiota. The microbiota is a source of gene products that are required for several functions linked to digestion and energy harvest, thus it has to be tolerated, but at the same time controlled. We have shown that the capacity to tolerate the microbiota is linked to a close interaction between epithelial cells, that are the first line of defence against luminal microorganisms, and specialized immune cells called dendritic cells, that acquire a tolerogenic phenotype and drive the development of T regulatory cells, capable to control the development of inflammatory responses to bacteria. We have identified several effectors mediating this control and focused on a cytokine called thymic stromal lymphopoietin (TSLP) that is released constitutively by epithelial cells and is strongly downregulated in inflammatory bowel disease (IBD). By contrast, in other inflammatory disorders like allergy or asthma, TSLP has been shown to be upregulated and to mediate disease. This apparent controversy is solved when considering that TSLP comes in two different isoforms: a short (sTSLP) and a long (lTSLP). sTSLP has been completely neglected in the literature as most of the reagents do not distinguish it from lTSLP. Within the ERC project Dendroworld, we have generated all the tools to study the function of these two isoforms. We discovered that in IBD there is an inverse correlation between sTSLP and lTSLP. lTSLP is drastically upregulated by recruited immune cells, while sTSLP is downregulated in epithelial cells. Hence, we hypothesized and confirmed that the two isoforms had different activities, with the sTSLP being anti-inflammatory and lTSLP being inflammatory. In this POC we propose scientific and commercialization activities to bring sTSLP to the market as a new class of anti-inflammatory drugs capable of re-establishing immune homeostasis.'