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Query: UMLS:C0019621 (
Langerhans cell histiocytosis
)
3,250
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
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.
...
PMID:Notch is active in Langerhans cell histiocytosis and confers pathognomonic features on dendritic cells. 2307 78
Langerhans cell histiocytosis
(
LCH
) is a MAPK pathway-driven disease characterized by the accumulation of CD1a
+
langerin
+
cells of unknown origin. We have previously reported that the Notch signaling pathway is active in
LCH
lesions and that the Notch ligand
Jagged2
(
JAG2
) induces CD1a and langerin expression in monocytes in vitro. Here we show that Notch signaling induces monocytes to acquire an
LCH
gene signature and that Notch inhibition suppresses the
LCH
phenotype. In contrast, while also CD1c
+
dendritic cells or IL-4-stimulated CD14
+
monocytes acquire CD1a and langerin positivity in culture, their gene expression profiles and surface phenotypes are more different from primary
LCH
cells. We propose a model where CD14
+
monocytes serve as
LCH
cell precursor and
JAG2
-mediated activation of the Notch signaling pathway initiates a differentiation of monocytes toward
LCH
cells in selected niches and thereby contributes to
LCH
pathogenesis.
...
PMID:JAG2 signaling induces differentiation of CD14
+
monocytes into Langerhans cell histiocytosis-like cells. 3029 38
