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| Status |
Public on Jan 21, 2020 |
| Title |
Circulating CD1c+ myeloid dendritic cells are precursors to Langerhans cell histiocytosis (LCH) lesion CD1a+CD207+cells |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
|
| Summary |
Expression data from LCH lesion subpopulations and healthy donors' peripheral blood specimens
Langerhans cell histiocytosis (LCH) is a myeloproliferative disorder that is characterized by the inflammatory lesions with pathogenic CD1a+CD207+ dendritic cells (DCs). BRAFV600E and other somatic activating MAPK gene mutations have been identified in differentiating bone marrow and blood myeloid cells, but the origin of the LCH lesion CD1a+CD207+DCs and mechanisms of lesion formation remain incompletely defined. In order to identify candidate LCH CD1a+CD207+DCs’ precursor populations, gene expression profiles of LCH lesion CD1a+CD207+DCs were first compared to established gene signatures from human myeloid cell subpopulations. Interestingly, the CD1c+ myeloid DC (mDC) gene signature was most enriched in the LCH CD1a+CD207+DC’ transcriptome. Additionally, the BRAFV600E allele was not only localized to CD1a+CD207-DCs and CD1a+CD207+DCs, but it was also identified in CD1c+mDCs in LCH lesions. Transcriptomes of CD1a+CD207-DCs were nearly indistinguishable from CD1a+CD207+DCs (both CD207low and CD207high subpopulations). Transcription profiles of LCH lesion CD1a+CD207+DCs and peripheral blood CD1c+mDCs from healthy donors were compared to identify potential LCH DC-specific biomarkers. HLADQB2 expression was significantly increased in LCH lesion CD1a+CD207+DCs compared to circulating CD1c+mDCs from healthy donors, and HLA-DQB2 antigen was identified on LCH lesion CD1a+CD207- and CD1a+CD207+DCs as well as on CD1c+(CD1a+CD207-) mDCs, but not in any other lesion myeloid subpopulations. Interestingly, HLADQB2 expression was specific to peripheral blood of patients with BRAFV600E+ peripheral blood mononuclear cells (PBMC), and HLA-DQB2+CD1c+blood cells were highly enriched for the BRAFV600E in these patients. These data support a model where blood CD1c+mDCs with activated ERK migrate to lesion sites where they differentiate into pathogenic CD1a+CD207+ DCs.
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| Overall design |
57 samples: 18 healthy donor peripheral blood/skin subpopulations and 39 LCH lesion subpopulation specimens
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| Contributor(s) |
Lim K, Milne P, Ginhoux F, Collin M, Allen C |
| Citation(s) |
31899802 |
| Submission date |
Nov 13, 2018 |
| Last update date |
Jan 21, 2020 |
| Contact name |
Carl Allen |
| E-mail(s) |
ceallen@bcm.edu
|
| Organization name |
Baylor College of Medicine
|
| Department |
Department of Pediatrics- Cancer
|
| Lab |
Histiocytosis Research Lab
|
| Street address |
1102 Bates Street, C1024.25
|
| City |
Houston |
| State/province |
TX |
| ZIP/Postal code |
77030 |
| Country |
USA |
| |
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| Platforms (1) |
| GPL17586 |
[HTA-2_0] Affymetrix Human Transcriptome Array 2.0 [transcript (gene) version] |
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| Samples (57)
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| Relations |
| BioProject |
PRJNA505325 |
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