'Iron'ing out hemophagocytosis through PIEZO1
| Autor: | Neil A. Hanchard, Ambroise Wonkam |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Aging
Erythrocytes Iron Overload Iron Cell Biology Mechanotransduction Cellular General Biochemistry Genetics and Molecular Biology Article Ion Channels Cohort Studies Mice 03 medical and health sciences 0302 clinical medicine Iron homeostasis Hepcidins Phagocytosis Stress Physiological medicine Homeostasis Animals Humans Erythropoiesis Alleles 030304 developmental biology Malarial infection 0303 health sciences Macrophages PIEZO1 Malaria Black or African American Mice Inbred C57BL Red blood cell medicine.anatomical_structure Phenotype Gain of Function Mutation Immunology Erythrocyte Count Hepatocytes Hemophagocytosis 030217 neurology & neurosurgery |
| Zdroj: | Cell |
| Popis: | Iron overload causes progressive organ damage and is associated with diseases including arthritis, liver and heart failure. Elevated iron levels are present in 1–5% of individuals; however, iron overload is undermonitored and underdiagnosed. Genetic factors affecting iron homeostasis are emerging. Individuals with hereditary xerocytosis, a rare disorder with gain-of-function (GOF) mutations in mechanosensitive PIEZO1 ion channel, develop age-onset iron overload. We show that constitutive or macrophage expression of a GOF Piezo1 allele in mice disrupts levels of the iron regulator hepcidin and causes iron overload. We further show that PIEZO1 is a key regulator of macrophage phagocytic activity and subsequent erythrocyte turnover. Strikingly, we find that E756del, a mild GOF PIEZO1 allele present in a third of individuals of African descent, is strongly associated with increased plasma iron. Our study links macrophage mechanotransduction to iron metabolism and identifies a genetic risk factor for increased iron level in African Americans. |
| Databáze: | OpenAIRE |
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