Essential role of the microglial triggering receptor expressed on myeloid cells-2 (TREM2) for central nervous tissue immune homeostasis

Neumann, Harald; Takahashi, Kazuya

doi:10.1016/j.jneuroim.2006.11.032

Cited by 227 publications

(176 citation statements)

References 43 publications

Supporting

Mentioning

164

Contrasting

Unclassified

Order By: Relevance

“…Surprisingly, we found that subsets of microglia were the only cells expressing Trem2 within the healthy adult murine CNS as assayed by in situ hybridization analysis in previously published studies [15]. Subsequent studies of adult rodent tissue have confirmed these initial findings [16][17][18]. In addition, Kiialainen et al have observed by immunostaining that not all microglia in mixed glial cultures express detectable levels of Trem2 and DAP12 [19].…”

Section: Introductionsupporting

confidence: 80%

Developmental Regulation of TREM2 and DAP12 Expression in the Murine CNS: Implications for Nasu-Hakola Disease

Thrash

Torbett

2008

Neurochem Res

View full text Add to dashboard Cite

Trem2 is an orphan, DAP12 associated receptor constitutively expressed in vivo by subsets of microglia in the healthy adult murine CNS and in vitro by subsets of oligodendrocytes in neonatal mixed glial cultures. Loss of a functional Trem2 signaling pathway is the genetic cause of NasuHakola disease. Whether the early onset cognitive dementia and myelin-pallor associated with this disorder are due to deficits in functional Trem2 signaling in microglia and/or oligodendrocytes is still being debated. Here, we find that Trem2/DAP12 expression is detected in embryonic day 14 CNS mRNA. Using dual immunohistochemistry/in situ hybridization, we find that both Trem2 and DAP12 expression always co-localized with markers of microglia/macrophages. However, Trem2/ DAP12 positive microglia are found in very close apposition with CNP+ oligodendrocytes prior to myelination (post-natal day 1). In addition, CNS expression of TREM2 and DAP12 are not detected in PU.1KO which lack microglia and macrophages. Our data provide continuing support for NasuHakola disease being identified as a cognitive disorder caused by a primary dysfunction of CNS microglia.

show abstract

Section: Introductionsupporting

confidence: 80%

Developmental Regulation of TREM2 and DAP12 Expression in the Murine CNS: Implications for Nasu-Hakola Disease

Thrash

Torbett

2008

Neurochem Res

View full text Add to dashboard Cite

show abstract

“…In both models, peripheral, hematopoietic side effects are likely the main contributing factors of the lethal phenotype. Nevertheless, long-term elimination or dysfunction of microglia likely has deleterious consequences on CNS homeostasis as exemplified in neurodegenerative conditions, such as Nasu-Hakola disease or Rett syndrome (22,33,34).…”

Section: Discussionmentioning

confidence: 99%

Microglial repopulation model reveals a robust homeostatic process for replacing CNS myeloid cells

Varvel

Grathwohl

Baumann

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

212

206

View full text Add to dashboard Cite

Under most physiological circumstances, monocytes are excluded from parenchymal CNS tissues. When widespread monocyte entry occurs, their numbers decrease shortly after engraftment in the presence of microglia. However, some disease processes lead to focal and selective loss, or dysfunction, of microglia, and microglial senescence typifies the aged brain. In this regard, the long-term engraftment of monocytes in the microglia-depleted brain remains unknown. Here, we report a model in which a niche for myeloid cells was created through microglia depletion. We show that microglia-depleted brain regions of CD11b-HSVTK transgenic mice are repopulated with new Iba-1-positive cells within 2 wk. The engrafted cells expressed high levels of CD45 and CCR2 and appeared in a wave-like pattern frequently associated with blood vessels, suggesting the engrafted cells were peripheral monocytes. Although two times more numerous and morphologically distinct from resident microglia up to 27 wk after initial engraftment, the overall distribution of the engrafted cells was remarkably similar to that of microglia. Two-photon in vivo imaging revealed that the engrafted myeloid cells extended their processes toward an ATP source and displayed intracellular calcium transients. Moreover, the engrafted cells migrated toward areas of kainic acid-induced neuronal death. These data provide evidence that circulating monocytes have the potential to occupy the adult CNS myeloid niche normally inhabited by microglia and identify a strong homeostatic drive to maintain the myeloid component in the mature brain.chemokines | myeloid cell heterogeneity | neuroinflammation | in vivo calcium imaging

show abstract

“…N'Diaye et al [130] transfected a Trem2-DAP12 fusion construct into normally nonphagocytic Chinese hamster ovary cells and found that this was sufficient to induce phagocytic uptake of Escherichia coli bioparticles. Trem2 activation has also been shown to promote anti-inflammatory cytokine production, reduce proinflammatory cytokine production [131], and enhance chemotaxis via upregulation of CCR7 in various immune cell types [132]. While these in vitro studies have determined some of the signaling components involved and possible functional outcomes of Trem2 signaling, these results need to be confirmed and expanded in an in vivo context.…”

Section: Trem2/trem2 Ligandmentioning

confidence: 99%

The Evolving Biology of Microglia in Alzheimer's Disease

2015

View full text Add to dashboard Cite

Essential role of the microglial triggering receptor expressed on myeloid cells-2 (TREM2) for central nervous tissue immune homeostasis

Cited by 227 publications

References 43 publications

Developmental Regulation of TREM2 and DAP12 Expression in the Murine CNS: Implications for Nasu-Hakola Disease

Developmental Regulation of TREM2 and DAP12 Expression in the Murine CNS: Implications for Nasu-Hakola Disease

Microglial repopulation model reveals a robust homeostatic process for replacing CNS myeloid cells

The Evolving Biology of Microglia in Alzheimer's Disease

Contact Info

Product

Resources

About