Increased AXLhigh myeloid cells as pathognomonic marker in Langerhans cell histiocytosis and Langerin expression dependence of mTOR inhibition.
Clin Immunol
; 263: 110203, 2024 Jun.
Article
em En
| MEDLINE
| ID: mdl-38575046
ABSTRACT
Langerhans cell histiocytosis (LCH) is characterized by an expansion and accumulation of pathological histiocytes expressing langerin (CD207) and CD1a in different organs under an inflammatory milieu. The origin of pathognomonic precursors of LCH is widely debated, but monocytes and pre-dendritic cells (pre-DC) play a significant role. Remarkably, we found an expansion of AXLhigh cells in the CD11c+ subset of patients with active LCH, which also express the pathognomonic CD207 and CD1a. Moreover, we obtained a monocyte-derived LC-like (mo-LC-like) expressing high levels of AXL when treated with inflammatory cytokine, or plasma of patients with active disease. Intriguingly, inhibiting the mTOR pathway at the initial stages of monocyte differentiation to LC-like fosters the pathognomonic LCH program, highly increasing CD207 levels, together with NOTCH1 induction. We define here that AXLhigh could also be taken as a strong pathognomonic marker for LCH, and the release of Langerin and NOTCH1 expression depends on the inhibition of the mTOR pathway.
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Base de dados:
MEDLINE
Assunto principal:
Antígenos CD
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Histiocitose de Células de Langerhans
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Proteínas Proto-Oncogênicas
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Receptores Proteína Tirosina Quinases
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Lectinas Tipo C
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Lectinas de Ligação a Manose
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Serina-Treonina Quinases TOR
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Receptor Tirosina Quinase Axl
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article