DAP12 signaling: from immune cells to bone modeling and brain myelination

Colonna, Marco

doi:10.1172/jci200317745

Cited by 6 publications

(6 citation statements)

References 15 publications

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“…TREM2 is thus an anti‐inflammatory receptor that at the same time promotes phagocytic activity. TREM2 is intracellularly coupled to the adapter protein DAP12 [for review see: (Linnartz et al, )], and interestingly, loss of function mutations of either TREM2 or DAP12 lead to a rare chronic neurodegenerative disease known as Nasu‐Hakola or polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy (PLOSL) (Colonna, ).…”

Section: Addressing Microglia Functionmentioning

confidence: 99%

What is microglia neurotoxicity (Not)?

Biber

Owens

Boddeke

2014

Glia

132

109

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Microglia most likely appeared early in evolution as they are not only present in vertebrates, but are also found in nervous systems of various nonvertebrate organisms. Mammalian microglia are derived from a specific embryonic, self-renewable myeloid cell population that is throughout lifetime not replaced by peripheral myeloid cells. These phylogenic and ontogenic features suggest that microglia serve vital functions. Yet, microglia often are described as neurotoxic cells, that actively kill (healthy) neurons. Since it is from an evolutionary point of view difficult to understand why an important and vulnerable organ like the brain should host numerous potential killers, we here review the concept of microglia neurotoxicity. On one hand it is discussed that most of our understanding about how microglia kill neurons is based on in vitro experiments or correlative staining studies that suffer from the difficulty to discriminate microglia and peripheral myeloid cells in the diseased brain. On the other hand it is described that a more functional approach by mutating, inactivating or deleting microglia is seldom associated with a beneficial outcome in an acute injury situation, suggesting that microglia are normally important protective elements in the brain. This might change in chronic disease or the aged brain, where; however, it remains to be established whether microglia simply lose their protective capacities or whether microglia become truly neurotoxic cells.

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Section: Addressing Microglia Functionmentioning

confidence: 99%

What is microglia neurotoxicity (Not)?

Biber

Owens

Boddeke

2014

Glia

132

109

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“…QuSAGE of the C2 canonical pathway gene sets from MSigDB (40) also reveals this network as a top hit (Supplemental Figure 6A). TYROBP, also called DAP12, is a transmembrane adaptor that links myeloid surface receptors to downstream signaling effectors (41). The current network annotation does not include a major upstream regulator of TYROBP, the transmembrane receptor TREM2 (24), nor its downstream signaling cascade centered on SYK (24), which includes NLRP3 activation (42) (Figure 5A).…”

Section: Impaired Adipokine Secretion In Chronic Adipose Tissue Response To Rtmentioning

confidence: 99%

Therapeutic radiation exposure of the abdomen during childhood induces chronic adipose tissue dysfunction

et al. 2021

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“…Very recently, another molecule involved in T-cell interaction with DCs has been shown to also affect bone. DAP12 is an adapter molecule involved in the transduction of activating signals for a range of immune cells, including NK cells, granulocytes, monocyte/macrophages and DCs, and DAP12-deficient mice have impaired T H 1 responses (reviewed in [28]). These mice have now been shown to have osteopetrosis, due to an inability of marrow precursors to differentiate to mature, resorptive osteoclasts [29].…”

Section: T-cell Interaction With Dendritic Cellsmentioning

confidence: 99%

“…These mice have now been shown to have osteopetrosis, due to an inability of marrow precursors to differentiate to mature, resorptive osteoclasts [29]. Current evidence suggests a model in which DAP12 may modulate responsiveness to certain cytokines, favouring osteoclast formation under normal conditions but promoting the differentiation of precursors to macrophages and the DC lineage in inflammatory conditions [28].…”

Section: T-cell Interaction With Dendritic Cellsmentioning

confidence: 99%