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CSF1R regulates the dendritic cell pool size in adult mice via embryo-derived tissue-resident macrophages
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CSF1R regulates the dendritic cell pool size in adult mice via embryo-derived tissue-resident macrophages
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Journal Article
CSF1R regulates the dendritic cell pool size in adult mice via embryo-derived tissue-resident macrophages
2018
Overview
Regulatory mechanisms controlling the pool size of spleen dendritic cells (DC) remain incompletely understood. DCs are continuously replenished from hematopoietic stem cells, and FLT3-mediated signals cell-intrinsically regulate homeostatic expansion of spleen DCs. Here we show that combining FLT3 and CSF1R-deficiencies results in specific and complete abrogation of spleen DCs in vivo. Spatiotemporally controlled CSF1R depletion reveals a cell-extrinsic and non-hematopoietic mechanism for DC pool size regulation. Lack of CSF1R-mediated signals impedes the differentiation of spleen macrophages of embryonic origin, and the resulted macrophage depletion during development or in adult mice results in loss of DCs. Moreover, embryo-derived macrophages are important for the physiologic regeneration of DC after activation-induced depletion in situ. In summary, we show that the differentiation of DC and their regeneration relies on ontogenetically distinct spleen macrophages, thereby providing a novel regulatory principle that may also be important for the differentiation of other hematopoietic cell types.
Dendritic cells (DC) are important regulators of both innate and adaptive immunity, but how the DC pool is homeostatically maintained in vivo is unclear. Here the authors show that combined deficiency of FLT3 and CSF1R impedes the differentiation of spleen macrophages of embryonic origin that are required for DC homeostasis.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 13/31
/ 64/60
/ Animals
/ Dendritic Cells - metabolism
/ Embryos
/ Female
/ fms-Like Tyrosine Kinase 3 - genetics
/ fms-Like Tyrosine Kinase 3 - metabolism
/ Humanities and Social Sciences
/ Male
/ Mice
/ Receptors, Granulocyte-Macrophage Colony-Stimulating Factor - genetics
/ Receptors, Granulocyte-Macrophage Colony-Stimulating Factor - metabolism
/ Regulatory mechanisms (biology)
/ Rodents
/ Science
/ Spleen
