Abstract
Tissue-resident macrophages form an essential part of the first line of defense in all tissues of the body. Next to their immunological role, they play an important role in maintaining tissue homeostasis. Recently, it was shown that they are primarily of embryonic origin. During embryogenesis, precursors originating in the yolk sac and fetal liver colonize the embryonal tissues where they develop into mature tissue-resident macrophages. Their development is governed by two distinct sets of transcription factors. First, in the pre-macrophage stage, a core macrophage program is established by lineage-determining transcription factors. Under the influence of tissue-specific signals, this core program is refined by signal-dependent transcription factors. This nurturing by the niche allows the macrophages to perform tissue-specific functions. In the last 15 years, some of these niche signals and transcription factors have been identified. However, detailed insight in the exact mechanism of development is still lacking.
Highlights
Tissue-resident macrophages were first described by the Russian scientist Élie Metchnikoff in 1883 [1]
Tissue-resident macrophages located in the brain, called microglia, are small star-shaped cells with an extensive lamellipodial network and while they are involved in brain surveillance by constantly probing the cellular environment, they are crucial for brain development and homeostasis by regulating the synaptic pruning during postnatal development [12,13,14]
Other transcription factor ⁎ Corresponding authors at (TF) linked to tissue-resident macrophage development include Liver X receptor α (LXRα) and SPIC, these might be necessary for functional specialization, as no apparent defect in Kupffer cell abundance has been described in KO models involving these TFs [45,55]
Summary
Tissue-resident macrophages were first described by the Russian scientist Élie Metchnikoff in 1883 [1]. Tissue-resident macrophages located in the brain, called microglia, are small star-shaped cells with an extensive lamellipodial network and while they are involved in brain surveillance by constantly probing the cellular environment, they are crucial for brain development and homeostasis by regulating the synaptic pruning during postnatal development [12,13,14]. Another example are the lung alveolar macrophages which are involved in the clearance of alveolar surfactant [15]. We will discuss the signal-dependent TFs which adapt this core program in response to environmental cues, allowing macrophage to perform tissue-specific functions
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