期刊
JOURNAL OF EXPERIMENTAL MEDICINE
卷 208, 期 2, 页码 227-234出版社
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.20101459
关键词
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资金
- Medical Research Council (MRC)
- Wellcome Intermediate Fellowship
- LLR Bennett Senior Fellowship in Experimental Haematology
- BBSRC [BB/E012841/1] Funding Source: UKRI
- MRC [G0800358, G0701897] Funding Source: UKRI
- Biotechnology and Biological Sciences Research Council [BB/E012841/1] Funding Source: researchfish
- Medical Research Council [G0800358, G0701897] Funding Source: researchfish
Congenital or acquired cellular deficiencies in humans have the potential to reveal much about normal hematopoiesis and immune function. We show that a recently described syndrome of monocytopenia, B and NK lymphoid deficiency additionally includes the near absence of dendritic cells. Four subjects showed severe depletion of the peripheral blood HLA-DR+ lineage(-)compartment, with virtually no CD123(+) or CD11c(+) dendritic cells (DCs) and very few CD14(+) or CD16(+) monocytes. The only remaining HLA-DR+ lineage(-) cells were circulating CD34(+) progenitor cells. Dermal CD14(+) and CD1a(+) DC were also absent, consistent with their dependence on blood-derived precursors. In contrast, epidermal Langerhans cells and tissue macrophages were largely preserved. Combined loss of peripheral DCs, monocytes, and B and NK lymphocytes was mirrored in the bone marrow by complete absence of multilymphoid progenitors and depletion of granulocyte-macrophage progenitors. Depletion of the HLA-DR+ peripheral blood compartment was associated with elevated serum fms-like tyrosine kinase ligand and reduced circulating CD4(+)CD25(hi)FoxP3(+) T cells, supporting a role for DC in T reg cell homeostasis.
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