Thymic macrophages consist of two populations with distinct localization and origin
- National Yang Ming Chiao Tung University, Taiwan
- Academia Sinica, Taiwan
- University of California, Berkeley, United States
Abstract
Tissue-resident macrophages are essential to protect from pathogen invasion and maintain organ homeostasis. The ability of thymic macrophages to engulf apoptotic thymocytes is well appreciated, but little is known about their ontogeny, maintenance, and diversity. Here, we characterized the surface phenotype and transcriptional profile of these cells and defined their expression signature. Thymic macrophages were most closely related to spleen red pulp macrophages and Kupffer cells and shared the expression of the transcription factor SpiC with these cells. Single-cell RNA sequencing showed that the macrophages in the adult thymus are composed of two populations distinguished by the expression of Timd4 and Cx3cr1. Remarkably, Timd4+ cells were located in the cortex, while Cx3cr1+ macrophages were restricted to the medulla and the cortico-medullary junction. Using shield chimeras, transplantation of embryonic thymuses, and genetic fate mapping, we found that the two populations have distinct origins. Timd4+ thymic macrophages are of embryonic origin, while Cx3cr1+ macrophages are derived from adult hematopoietic stem cells. Aging has a profound effect on the macrophages in the thymus. Timd4+ cells underwent gradual attrition, while Cx3cr1+ cells slowly accumulated with age and, in older mice, were the dominant macrophage population in the thymus. Altogether, our work defines the phenotype, origin, and diversity of thymic macrophages.
Data availability
The RNA Sequencing data of thymic macrophages and thymic dendritic cells are available at NCBI Gene Expression Omnibus (GEO) as part of GSE122108 and at www.immgen.org. The single cell RNA sequencing data is deposited at NCBI GEO under accession number GSE185460. The source data underlying Fig. 1G and H, Fig. 3B, D, and G, Fig. 5C, F, and I, Fig. 6B, E, G, and I, Fig. 7B, C, D, and G, Fig. 8B, D, E, and F, Fig. 1S4, Fig. 2S1, Fig. 2S2, Fig. 2S3, Fig. 5S1, and Fig. 5S2 are provided in the Source Data files. All other data supporting the findings of this study are available within the article.
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Single-cell RNA-sequencing of thymic myeloid cells from Csf1rgfp/gfp (MaFIA) and Cd11cyfp/yfp miceNCBI Gene Expression Omnibus, GSE185460.
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OpenSource Mononuclear Phagocytes ProjectNCBI Gene Expression Omnibus, GSE122108.
Article and author information
Author details
Funding
Ministry of Science and Technology, Taiwan (107-2320-B-010 -016 -MY3)
- Ivan L Dzhagalov
Ministry of Science and Technology, Taiwan (110-2320-B-A49A-521 -)
- Ivan L Dzhagalov
Ministry of Science and Technology, Taiwan (111-2320-B-A49 -031 -MY3)
- Ivan L Dzhagalov
Yen Tjing Ling Medical Foundation (CI-111-6)
- Ivan L Dzhagalov
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: All experimental procedures involving animals were approved by the Institutional Animal Care and Use Committee (IACUC) of National Yang Ming Chiao Tung University (animal protocols #1070506, and 1090301). All surgery was performed under Ketamine + Xylazine anesthesia, and every effort was made to minimize suffering.
Copyright
© 2022, Zhou et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Thymic macrophages consist of two populations with distinct localization and origin
eLife 11:e75148.
https://doi.org/10.7554/eLife.75148
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