Cited by 431Iron Metabolism and DisordersPhagocytosis and Immune RegulationHeme Oxygenase-1 and Carbon Monoxide

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Heme-Mediated SPI-C Induction Promotes Monocyte Differentiation into Iron-Recycling Macrophages

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Haldar, Malay, Kohyama, Masako, So, Alex Yick-Lun, KC, Wumesh, Wu, Xiaodi, Briseño, Carlos G., Satpathy, Ansuman T., Kretzer, Nicole M., Arase, Hisashi, Rajasekaran, Namakkal S., Wang, Li, Egawa, Takeshi, Igarashi, Kazuhiko, Baltimore, David, Murphy, Theresa L., Murphy, Kenneth M.·2014·Cell

DOI 10.1016/j.cell.2014.01.069PMC PMC4010949

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Abstract

Splenic red pulp macrophages (RPM) degrade senescent erythrocytes and recycle heme-associated iron. The transcription factor SPI-C is selectively expressed by RPM and is required for their development, but the physiologic stimulus inducing Spic is unknown. Here, we report that Spic also regulated the development of F4/80(+)VCAM1(+) bone marrow macrophages (BMM) and that Spic expression in BMM and RPM development was induced by heme, a metabolite of erythrocyte degradation. Pathologic hemolysis induced loss of RPM and BMM due to excess heme but induced Spic in monocytes to generate new RPM and BMM. Spic expression in monocytes was constitutively inhibited by the transcriptional repressor BACH1. Heme induced proteasome-dependent BACH1 degradation and rapid Spic derepression. Furthermore, cysteine-proline dipeptide motifs in BACH1 that mediate heme-dependent degradation were necessary for Spic induction by heme. These findings are the first example of metabolite-driven differentiation of a tissue-resident macrophage subset and provide new insights into iron homeostasis.

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Authors: Haldar, M., Kohyama, M., So, A. Y.-L., KC, W., Wu, X., Briseño, C. G., Satpathy, A. T., Kretzer, N. M., Arase, H., Rajasekaran, N. S., Wang, L., Egawa, T., Igarashi, K., Baltimore, D., Murphy, T. L., & Murphy, K. M.
Affiliations: Washington University in St. Louis (US)
Immunology Frontier Research Center, The University of Osaka (JP)
California Institute of Technology (US)
University of Utah (US)
Tohoku University (JP)
Howard Hughes Medical Institute (US)
Corresponding author: Murphy, Kenneth M.
ORCID: Haldar, Malay
KC, Wumesh
Wu, Xiaodi
Briseño, Carlos G.
Satpathy, Ansuman T.
Kretzer, Nicole M.
Arase, Hisashi
Rajasekaran, Namakkal S.
Egawa, Takeshi
Igarashi, Kazuhiko
Baltimore, David
Murphy, Kenneth M.
Venue: Cell
Publisher: Elsevier BV
Published: 2014-03
Volume: 156
Issue: 6
Pages: 1223-1234
ISSN: 0092-8674 (ISSN-L)
DOI: 10.1016/j.cell.2014.01.069
PMC: PMC4010949
OpenAlex: W2087101282
Cited by: 431
References: 48
Citations by year: 2026: 37 · 2025: 30 · 2024: 31 · 2023: 29 · 2022: 34 · 2021: 40 · 2020: 47 · 2019: 38 · 2018: 34 · 2017: 32 · 2016: 33 · 2015: 34 · 2014: 11
FWCI: 26.00
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 377 d)
Locations: Cell (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
CaltechAUTHORS (California Institute of Technology) (submittedVersion)
Funders: Howard Hughes Medical Institute
Japan Society for the Promotion of Science (24659223, 25670143)
National Heart, Lung, and Blood Institute (K99HL118754)
National Cancer Institute (T32 CA 9547-27, T32CA009547)
National Institute of Allergy and Infectious Diseases (AI076427-02, R01AI076427, R01AI097244, R01AI093531, K08AI106953, T32AI007163)
Topics: Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
Life Sciences › Immunology and Microbiology › Immunology › Phagocytosis and Immune Regulation
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Heme Oxygenase-1 and Carbon Monoxide
Keywords: heme, bone marrow-derived macrophages, monocyte differentiation, iron recycling, BACH1, proteasomal degradation, hemolysis, iron homeostasis, transcriptional repressor
MeSH terms: Animals, Bone Marrow Cells, Cell Differentiation, DNA-Binding Proteins, Female, Heme, Iron, Macrophages, Male, Mice, Inbred C57BL, Monocytes, Spleen, Myeloid Cells, Basic-Leucine Zipper Transcription Factors, Mice, Mice, 129 Strain

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Heme-Mediated SPI-C Induction Promotes Monocyte Differentiation into Iron-Recycling Macrophages

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