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 +CD25hiFoxP3+ T cells, supporting a role for DC in T reg cell homeostasis.

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The Journal of Experimental Medicine
Erasmus MC: University Medical Center Rotterdam

Bigley, V., Haniffa, . muzlifah ., Doulatov, S., Wang, X. N., Dickinson, R., McGovern, N., … Collin, M. (2011). The human syndrome of dendritic cell, monocyte, B and NK lymphoid deficiency. The Journal of Experimental Medicine, 208(2), 227–234. doi:10.1084/jem.20101459