Characterization of innate lymphoid cells in intestinal pathophysiology.
Description: Inflammatory Bowel Disease (IBD) is a chronic inflammatory disorder of the gut, encompassing Crohn's disease (CD) and ulcerative colitis (UC). Th-1 and Th-17 responses prevail in CD, while Th-17 and non-classical Th-2 responses are found in UC. Recent data suggest that innate lymphoid cells (ILC) may also contribute to chronic intestinal inflammation. Work from Prof Powrie's lab has identified IL23-responsive ILC that drive murine innate colitis through IL17A and IFNgamma production. We found ac cumulation of a similar population of CD56-CD127+ILC in the intestine of patients with CD. These cells respond to IL23, secrete IL17A and IFNgamma and phenotypically resemble foetal lymphoid tissue inducer cells. ILC that produce the Th-2 cytokines IL5 and IL13 have also been identified in mice and men, but their role in human intestinal inflammation is unknown. In this project we aim to further characterize the role of human intestinal ILC in the mucosal immune response. In particular we aim t o evaluate whether they may contribute to chronic intestinal inflammation through the interaction with stromal cells and the recruitment of other inflammatory cells to the gut. We hypothesize that ILC may play an important amplifying role in the pathogenesis of IBD representing a promising target for treatment.
Funder: Wellcome Trust
Amount: £239,500
Funding type: fellowship
Funder scheme: Postdoctoral Training Fellowship for Clinicians
Start date: 2015-12-01
End date: 2020-02-29
Investigator: Dr Alessandra Geremia
Institution: University of Oxford
Funded outputs count: 8
Funder award ID: 101734/Z/13/Z
OpenAlex ID: G7752804985