Origin, fate and dynamics of macrophages at central nervous system interfaces

Tobias Goldmann; Peter Wieghofer; Marta Joana Costa Jordão; Fabiola Prutek; Nora Hagemeyer; Kathrin Frenzel; Lukas Amann; Ori Staszewski; Katrin Kierdorf; Martin Krueger; Giuseppe Locatelli; Hannah Hochgerner; Robert Zeiser; Slava Epelman; Frederic Geissmann; Josef Priller; Fabio M.V. Rossi; Ingo Bechmann; Martin Kerschensteiner; Sten Linnarsson; Steffen Jung; Marco Prinz

doi:10.1038/ni.3423

Origin, fate and dynamics of macrophages at central nervous system interfaces

Tobias Goldmann, Peter Wieghofer, Marta Joana Costa Jordão, Fabiola Prutek, Nora Hagemeyer, Kathrin Frenzel, Lukas Amann, Ori Staszewski, Katrin Kierdorf, Martin Krueger, Giuseppe Locatelli, Hannah Hochgerner, Robert Zeiser, Slava Epelman, Frederic Geissmann, Josef Priller, Fabio M.V. Rossi, Ingo Bechmann, Martin Kerschensteiner, Sten LinnarssonSteffen Jung, Marco Prinz

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Abstract

Perivascular, subdural meningeal and choroid plexus macrophages are non-parenchymal macrophages that mediate immune responses at brain boundaries. Although the origin of parenchymal microglia has recently been elucidated, much less is known about the precursors, the underlying transcriptional program and the dynamics of the other macrophages in the central nervous system (CNS). It was assumed that they have a high turnover from blood-borne monocytes. However, using parabiosis and fate-mapping approaches in mice, we found that CNS macrophages arose from hematopoietic precursors during embryonic development and established stable populations, with the notable exception of choroid plexus macrophages, which had dual origins and a shorter life span. The generation of CNS macrophages relied on the transcription factor PU.1, whereas the MYB, BATF3 and NR4A1 transcription factors were not required.

Original language	English
Pages (from-to)	797-805
Number of pages	9
Journal	Nature Immunology
Volume	17
Issue number	7
DOIs	https://doi.org/10.1038/ni.3423
State	Published - 21 Jun 2016
Externally published	Yes

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Goldmann, T., Wieghofer, P., Jordão, M. J. C., Prutek, F., Hagemeyer, N., Frenzel, K., Amann, L., Staszewski, O., Kierdorf, K., Krueger, M., Locatelli, G., Hochgerner, H., Zeiser, R., Epelman, S., Geissmann, F., Priller, J., Rossi, F. M. V., Bechmann, I., Kerschensteiner, M., ... Prinz, M. (2016). Origin, fate and dynamics of macrophages at central nervous system interfaces. Nature Immunology, 17(7), 797-805. https://doi.org/10.1038/ni.3423

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title = "Origin, fate and dynamics of macrophages at central nervous system interfaces",

abstract = "Perivascular, subdural meningeal and choroid plexus macrophages are non-parenchymal macrophages that mediate immune responses at brain boundaries. Although the origin of parenchymal microglia has recently been elucidated, much less is known about the precursors, the underlying transcriptional program and the dynamics of the other macrophages in the central nervous system (CNS). It was assumed that they have a high turnover from blood-borne monocytes. However, using parabiosis and fate-mapping approaches in mice, we found that CNS macrophages arose from hematopoietic precursors during embryonic development and established stable populations, with the notable exception of choroid plexus macrophages, which had dual origins and a shorter life span. The generation of CNS macrophages relied on the transcription factor PU.1, whereas the MYB, BATF3 and NR4A1 transcription factors were not required.",

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Goldmann, T, Wieghofer, P, Jordão, MJC, Prutek, F, Hagemeyer, N, Frenzel, K, Amann, L, Staszewski, O, Kierdorf, K, Krueger, M, Locatelli, G, Hochgerner, H, Zeiser, R, Epelman, S, Geissmann, F, Priller, J, Rossi, FMV, Bechmann, I, Kerschensteiner, M, Linnarsson, S, Jung, S & Prinz, M 2016, 'Origin, fate and dynamics of macrophages at central nervous system interfaces', Nature Immunology, vol. 17, no. 7, pp. 797-805. https://doi.org/10.1038/ni.3423

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AU - Goldmann, Tobias

AU - Wieghofer, Peter

AU - Jordão, Marta Joana Costa

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AU - Hagemeyer, Nora

AU - Frenzel, Kathrin

AU - Amann, Lukas

AU - Staszewski, Ori

AU - Kierdorf, Katrin

AU - Krueger, Martin

AU - Locatelli, Giuseppe

AU - Hochgerner, Hannah

AU - Zeiser, Robert

AU - Epelman, Slava

AU - Geissmann, Frederic

AU - Priller, Josef

AU - Rossi, Fabio M.V.

AU - Bechmann, Ingo

AU - Kerschensteiner, Martin

AU - Linnarsson, Sten

AU - Jung, Steffen

AU - Prinz, Marco

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AB - Perivascular, subdural meningeal and choroid plexus macrophages are non-parenchymal macrophages that mediate immune responses at brain boundaries. Although the origin of parenchymal microglia has recently been elucidated, much less is known about the precursors, the underlying transcriptional program and the dynamics of the other macrophages in the central nervous system (CNS). It was assumed that they have a high turnover from blood-borne monocytes. However, using parabiosis and fate-mapping approaches in mice, we found that CNS macrophages arose from hematopoietic precursors during embryonic development and established stable populations, with the notable exception of choroid plexus macrophages, which had dual origins and a shorter life span. The generation of CNS macrophages relied on the transcription factor PU.1, whereas the MYB, BATF3 and NR4A1 transcription factors were not required.

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Origin, fate and dynamics of macrophages at central nervous system interfaces

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