Circulating CD1c+ myeloid dendritic cells are potential precursors to LCH lesion CD1a+CD207+ cells.

Autor: Lim KPH; Texas Children's Cancer Center, Texas Children's Hospital, Houston, TX.; Division of Pediatric Hematology-Oncology, Department of Pediatrics, and.; Graduate Program in Translational Biology and Molecular Medicine, College of Medicine, Baylor University, Houston, TX., Milne P; Human Dendritic Cell Laboratory, Newcastle University, Newcastle upon Tyne, United Kingdom., Poidinger M; Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR), Singapore., Duan K; Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR), Singapore., Lin H; Texas Children's Cancer Center, Texas Children's Hospital, Houston, TX.; Division of Pediatric Hematology-Oncology, Department of Pediatrics, and., McGovern N; Department of Pathology, University of Cambridge, Cambridge, United Kingdom., Abhyankar H; Texas Children's Cancer Center, Texas Children's Hospital, Houston, TX.; Division of Pediatric Hematology-Oncology, Department of Pediatrics, and., Zinn D; Texas Children's Cancer Center, Texas Children's Hospital, Houston, TX.; Division of Pediatric Hematology-Oncology, Department of Pediatrics, and., Burke TM; Texas Children's Cancer Center, Texas Children's Hospital, Houston, TX.; Division of Pediatric Hematology-Oncology, Department of Pediatrics, and.; Graduate Program in Translational Biology and Molecular Medicine, College of Medicine, Baylor University, Houston, TX.; Medical Scientist Training Program, College of Medicine, Baylor University, Houston, TX; and., Eckstein OS; Texas Children's Cancer Center, Texas Children's Hospital, Houston, TX.; Division of Pediatric Hematology-Oncology, Department of Pediatrics, and., Chakraborty R; Texas Children's Cancer Center, Texas Children's Hospital, Houston, TX.; Division of Pediatric Hematology-Oncology, Department of Pediatrics, and., Sengal A; Texas Children's Cancer Center, Texas Children's Hospital, Houston, TX.; Division of Pediatric Hematology-Oncology, Department of Pediatrics, and., Scull B; Texas Children's Cancer Center, Texas Children's Hospital, Houston, TX.; Division of Pediatric Hematology-Oncology, Department of Pediatrics, and., Newell E; Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR), Singapore., Merad M; Icahn School of Medicine at Mount Sinai, New York, NY., McClain KL; Texas Children's Cancer Center, Texas Children's Hospital, Houston, TX.; Division of Pediatric Hematology-Oncology, Department of Pediatrics, and., Man TK; Texas Children's Cancer Center, Texas Children's Hospital, Houston, TX.; Division of Pediatric Hematology-Oncology, Department of Pediatrics, and., Ginhoux F; Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR), Singapore., Collin M; Human Dendritic Cell Laboratory, Newcastle University, Newcastle upon Tyne, United Kingdom., Allen CE; Texas Children's Cancer Center, Texas Children's Hospital, Houston, TX.; Division of Pediatric Hematology-Oncology, Department of Pediatrics, and.; Graduate Program in Translational Biology and Molecular Medicine, College of Medicine, Baylor University, Houston, TX.
Jazyk: angličtina
Zdroj: Blood advances [Blood Adv] 2020 Jan 14; Vol. 4 (1), pp. 87-99.
DOI: 10.1182/bloodadvances.2019000488
Abstrakt: 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. To identify candidate LCH CD1a+CD207+ DC precursor populations, gene-expression profiles of LCH lesion CD1a+CD207+ DCs were first compared with 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 CD1a+CD207low and CD1a+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: HLA-DQB2 expression was significantly increased in LCH lesion CD1a+CD207+ DCs compared with circulating CD1c+ mDCs from healthy donors. HLA-DQB2 antigen was identified on LCH lesion CD1a+CD207- DCs and CD1a+CD207+ DCs as well as on CD1c+(CD1a+CD207-) mDCs, but it was not identified in any other lesion myeloid subpopulations. HLA-DQB2 expression was specific to peripheral blood of patients with BRAFV600E+ peripheral blood mononuclear cells, and HLA-DQB2+CD1c+ blood cells were highly enriched for the BRAFV600E in these patients. These data support a model in which blood CD1c+HLA-DQB2+ mDCs with activated ERK migrate to lesion sites where they differentiate into pathogenic CD1a+CD207+ DCs.
(© 2020 by The American Society of Hematology.)
Databáze: MEDLINE
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