Project

The role of prolyl hydroxylase 1 in innate and adaptive immunity, therapeutic implications for inflammatory bowel disease?

Duration
01 October 2017 → 30 September 2020
Funding
Research Foundation - Flanders (FWO)
Research disciplines
No data available
Keywords
IBD inflammatory bowel disease
 
Project description

Inflammatory bowel disease (IBD), including ulcerative colitis and Crohn's disease are chronic

relapsing disorders of the intestinal tract for which their is still no cure. Current treatment options

aim to suppress inflammation however there are a large number of patients that do not respond

or have a loss of response to treatment. Hence, there is a great need for new non-toxic therapies.

One appealling alternative approach is the inhibition of the oxygen sensing enzymes prolyl

hydroxylase 1, 2 and 3 which has been proven to be protective in experimental models for IBD.

However, due to the risk of unwanted side-effects their use in the clinic is hampered. Isoformspecific

targeting could represent a way to overcome these issues. In this regard, we showed that

the lack of prolyl hydroxylase 1 specifically in immune cells ameliorates the course of experimental

UC. However, some important questions still remain which we will address in the following

objectives:

1) Evaluate the therapeutic potential of specific Phd1 targeting in chronic models of colitis and

ileitis.

2) Assess the impact of Phd1 targeting on inflammation-linked intestinal complications (i.e. fibrosis

and colitis-associated cancer).

3) Dissect the mechanism(s) by which PHD1 targeting elicits anti-inflammatory properties by

analysing its effect in innate and and adaptive immune cells of healthy individuals and IBD

patients.