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

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.

Field of science

  • /social sciences/economics and business/business and management/commerce
  • /medical and health sciences/basic medicine/physiology/homeostasis
  • /humanities/languages and literature/literature - general
  • /medical and health sciences/clinical medicine/pneumology/asthma
  • /medical and health sciences/clinical medicine/allergology
  • /medical and health sciences/clinical medicine/gastroenterology/inflammatory bowel disease

Call for proposal

ERC-2012-PoC
See other projects for this call

Funding Scheme

CSA-SA(POC) - Supporting action (Proof of Concept)

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
€ 127 657
Administrative Contact
Ilaria Foti (Ms.)

Beneficiaries (2)

ISTITUTO EUROPEO DI ONCOLOGIA SRL
Italy
EU contribution
€ 127 657
Address
Via Filodrammatici 10
20121 Milano
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Administrative Contact
Ilaria Foti (Ms.)
IFOM FONDAZIONE ISTITUTO FIRC DI ONCOLOGIA MOLECOLARE
Italy
EU contribution
€ 19 260
Address
Via Adamello 16
20139 Milano
Activity type
Research Organisations
Administrative Contact
Carlo Raimondi Cominesi (Mr.)