Notch is active in Langerhans cell histiocytosis and confers pathognomonic features on dendritic cells.
Blood
; 120(26): 5199-208, 2012 Dec 20.
Article
em En
| MEDLINE
| ID: mdl-23074278
ABSTRACT
Langerhans cell histiocytosis (LCH) is an enigmatic disease defined by the accumulation of Langerhans cell-like dendritic cells (DCs). In the present study, we demonstrate that LCH cells exhibit a unique transcription profile that separates them not only from plasmacytoid and myeloid DCs, but also from epidermal Langerhans cells, indicating a distinct DC entity. Molecular analysis revealed that isolated and tissue-bound LCH cells selectively express the Notch ligand Jagged 2 (JAG2) and are the only DCs that express both Notch ligand and its receptor. We further show that JAG2 signaling induces key LCH-cell markers in monocyte-derived DCs, suggesting a functional role of Notch signaling in LCH ontogenesis. JAG2 also induced matrix-metalloproteinases 1 and 12, which are highly expressed in LCH and may account for tissue destruction in LCH lesions. This induction was selective for DCs and was not recapitulated in monocytes. The results of the present study suggest that JAG2-mediated Notch activation confers phenotypic and functional aspects of LCH to DCs; therefore, interference with Notch signaling may be an attractive strategy to combat this disease.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Células Dendríticas
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Histiocitose de Células de Langerhans
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Receptor Notch1
Limite:
Adolescent
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Child
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Child, preschool
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Female
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Humans
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Infant
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Male
Idioma:
En
Ano de publicação:
2012
Tipo de documento:
Article