CSF1R regulates the dendritic cell pool size in adult mice via embryo-derived tissue-resident macrophages

Gulce Itir Percin, Jiri Eitler, Andrea Kranz, Jun Fu, Jeffrey W. Pollard, Ronald Naumann, Claudia Waskow

Research output: Contribution to journalArticlepeer-review

Abstract

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.
Original languageEnglish
Article number5279
Number of pages12
JournalNature Communications
Volume9
DOIs
Publication statusPublished - 11 Dec 2018

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