Role for Spi-C in the development of red pulp macrophages and splenic iron homeostasis
Open accessAbstract
Tissue macrophages comprise a heterogeneous group of cell types differing in location, surface markers and function. Red pulp macrophages are a distinct splenic subset involved in removing senescent red blood cells. Transcription factors such as PU.1 (also known as Sfpi1) and C/EBPalpha (Cebpa) have general roles in myelomonocytic development, but the transcriptional basis for producing tissue macrophage subsets remains unknown. Here we show that Spi-C (encoded by Spic), a PU.1-related transcription factor, selectively controls the development of red pulp macrophages. Spi-C is highly expressed in red pulp macrophages, but not monocytes, dendritic cells or other tissue macrophages. Spic(-/-) mice have a cell-autonomous defect in the development of red pulp macrophages that is corrected by retroviral Spi-C expression in bone marrow cells, but have normal monocyte and other macrophage subsets. Red pulp macrophages highly express genes involved in capturing circulating haemoglobin and in iron regulation. Spic(-/-) mice show normal trapping of red blood cells in the spleen, but fail to phagocytose these red blood cells efficiently, and develop an iron overload localized selectively to splenic red pulp. Thus, Spi-C controls development of red pulp macrophages required for red blood cell recycling and iron homeostasis.
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Degradation of Bach1 induces expression of SpiC independently of Nrf2.
“Second, the degradation of Bach1 induces expression of the transcription factor (an E26 transformation-specific transcription factor of the Spi subfamily) SpiC independently of Nrf2 [116, 211].”
From “Pumping iron”—how macrophages handle iron at the systemic, microenvironmental, and cellular levels (2017) · cites this paper as [116]
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- Authors
- Kohyama, M., Ise, W., Edelson, B. T., Wilker, P. R., Hildner, K., Mejia, C., Frazier, W. A., Murphy, T. L., & Murphy, K. M.
- Affiliations
- Washington University in St. Louis (US)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Murphy, Kenneth M.
- Venue
- Nature
- Published
- 2008-11-26
- Volume
- 457
- Issue
- 7227
- Pages
- 318-321
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC2756102
- OpenAlex
- W2065338876
- Cited by
- 479
- References
- 30
- Citations by year
- 2026: 36 · 2025: 28 · 2024: 30 · 2023: 23 · 2022: 47 · 2021: 45 · 2020: 41 · 2019: 22 · 2018: 35 · 2017: 29 · 2016: 36 · 2015: 36 · 2014: 22 · 2013: 20 · 2012: 18
- FWCI
- 1.40
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- Howard Hughes Medical Institute
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Phagocytosis and Immune Regulation
- Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
- Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
- Keywords
- SPIC, red pulp macrophages, spleen, iron homeostasis, iron overload, erythrophagocytosis, senescent red blood cells, transcription factors
- MeSH terms
- Animals, Cell Count, DNA-Binding Proteins, Erythrocytes, Gene Expression Regulation, Homeostasis, Iron, Macrophages, Phagocytosis, Spleen, Vascular Cell Adhesion Molecule-1, Mice
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