Journal article
Induced disruption of the iron-regulatory hormone hepcidin inhibits acute inflammatory hypoferraemia
AE Armitage, PJ Lim, JN Frost, SR Pasricha, EJ Soilleux, E Evans, A Morovat, A Santos, R Diaz, D Biggs, B Davies, U Gileadi, PA Robbins, S Lakhal-Littleton, H Drakesmith
Journal of Innate Immunity | KARGER | Published : 2016
DOI: 10.1159/000447713
Abstract
Withdrawal of iron from serum (hypoferraemia) is a conserved innate immune antimicrobial strategy that can withhold this critical nutrient from invading pathogens, impairing their growth. Hepcidin (Hamp1) is the master regulator of iron and its expression is induced by inflammation. Mice lacking Hamp1 from birth rapidly accumulate iron and are susceptible to infection by blood-dwelling siderophilic bacteria such as Vibrio vulnificus. In order to study the innate immune role of hepcidin against a background of normal iron status, we developed a transgenic mouse model of tamoxifen-sensitive conditional Hamp1 deletion (termed iHamp1-KO mice). These mice attain adulthood with an iron status indi..
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Awarded by Wellcome Trust
Funding Acknowledgements
The authors thank Terry Rabbitts and Osama Al-Assar (WIMM, Oxford, UK) for providing Rosa-CreER<SUP>T2</SUP> mice; Craig Webster (Birmingham Heartlands Hospital, UK) for facilitating the acquisition of serum iron and Tsat data; the staff of the University of Oxford Department of Biomedical Services for animal husbandry; the staff of the Oxford Centre for Histopathology Research (OCHRe) for preparation of histology slides, and Vincenzo Cerundolo, Osama Al-Assar and Philip Hublitz (WIMM, Oxford, UK) for helpful advice and discussions. This work was supported by the Medical Research Council UK (MRC Centenary Award to A.E.A. and M.R.C. Human Immunology Unit core funding to H.D.), a Goodger and Schorstein Scholarship to A.E.A., the British Heart Foundation (Intermediate Science Research Fellowship to S.L.-L.) and by funding from Vifor Pharma to B.D., P.A.R. and S.L.-L. B.D., R.D., D.B. and A.S. were supported by Wellcome Trust Core Award Grant Number 090532/Z/09/Z.