Immune regulation of tissue iron in health and disease

PROJECT ABSTRACT
Anemia and inflammation often co-occur in chronic diseases including inflammatory bowel disease (IBD),
infection, and cancer. Anemia is often refractory to treatment in these diseases, and the impact of anemia and
anemia therapies on disease outcome is poorly defined. Accordingly, there is a significant medical need to
better understand the causal links between anemia and inflammatory diseases. One of the best defined links
between anemia and inflammation is a peptide hormone called hepcidin, which critically inhibits iron release
from intracellular stores. Hepcidin levels typically increase dramatically during inflammation, and can cause
one form of anemia termed anemia of inflammation (AI). Conversely, inflammatory diseases associated with
heavy bleeding cause a distinct form of anemia known as iron deficiency anemia (IDA), in which hepcidin
levels are suppressed. The fundamental focus of this research proposal is to: i.) investigate the impact
of hepcidin on inflammatory disease, ii.) identify cellular populations expressing hepcidin and its
partner ferroportin during inflammation, and iii.) determine the impact of iron modulation by distinct
cellular population on the resolution of inflammatory diseases. I will employ innovative technical
approaches and develop new tools to define the role of hepcidin and ferroportin during chemically-induced
intestinal damage, intestinal infection, and in inflammation-induced cancer. Collectively, results from these
studies will define the regulation and functional significance of novel cellular mediators of iron within
the intestine. These findings will critically inform ongoing efforts to develop therapies targeting tissue
repair and anemia in the context of inflammatory diseases.

Grant Number: 5DP2AI154440-05
NIH Institute/Center: NIH
Principal Investigator: Nicholas Bessman