The human syndrome of dendritic cell, monocyte, B and NK lymphoid deficiency

V Bigley, M Haniffa, S Doulatov, XN Wang, R Dickinson, N McGovern, L Jardine, S Pagan, I Dimmick, I Chua, J Wallis, J Lordan, C Morgan, DS Kumararatne, R Doffinger, Mirjam van der Burg, Jacques Dongen, A Cant, JE Dick, S HambletonM Collin

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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.
Original languageUndefined/Unknown
Pages (from-to)227-234
Number of pages8
JournalJournal of Experimental Medicine
Issue number2
Publication statusPublished - 2011

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