Role of Toll Like Receptor (TLR)-4 on iron homeostasis
Inflammatory bowel diseases (IBD), which include ulcerative colitis (UC) and Crohn’s disease (CD), are chronic inflammation of the gastrointestinal tract. Anaemia represents the most common complication in IBD, prevailing in 27% of patients with CD and 21% of patients UC. Anaemia is associated with poor quality of life, increased rate of hospitalization and deaths in IBD. Anaemia in patients with IBD arise due to iron deficiency anaemia (IDA) and anaemia of inflammation (AI). Most anaemic IBD patients are treated with iron supplementation, but half do not respond to iron supplementation therapies. We have discovered that leaky gut (endotoxemia) plays a key role in IBD induced anaemia (Bisht et al, unpublished data). We showed previously (Bisht et al, Fron in Immu, 2020) that endotoxin receptor, TLR4, is expressed by erythroblastic island macrophages, a crucial immune cell supporting red blood cell formation. However, role of TLR-4 on IBD induced anaemia is poorly understood. In this project, we aim to explore the role of TLR-4 on iron homeostasis in mouse model of colitis. We will specifically delete TLR-4 in erythroblastic island macrophages and tissue iron, iron homeostasis genes and proteins will be analysed.
The project will utilise mouse model of experiment colitis and mouse model of endotoxemia. Iron in liver, spleen and bone marrow will be analysed by Prussian blue and bathophenanthroline. Serum iron will be analysed using ELISA kit. Iron homeostasis genes in bone marrow, liver and duodenum will be analysed by quantitative real-time polymerase chain reaction.