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FLT3L governs the development of partially overlapping hematopoietic lineages in humans and mice (Single cell)

ABSTRACT: FMS-related tyrosine kinase 3 ligand (FLT3L), encoded by FLT3LG, is a hematopoietic growth factor essential for the development of lymphoid NK and B cells and myeloid dendritic cells (DCs) in mice. We describe three humans aged 28, 29, and 31 years who are homozygous for a frameshift FLT3LG variant. The cell-surface and secreted FLT3L isoforms encoded by these variants did not activate FLT3 in vitro. We detected no secreted FLT3L in the patients’ plasma or surface FLT3L on their T lymphocytes ex vivo. The patients’ bone marrow was hypoplastic, with globally low levels of hematopoietic progenitors, particularly myeloid precursors. Counts of platelets, red blood cells, granulocytes, and T and NK lymphocyte subsets in the patients’ blood were normal or near normal, whereas counts of B cells and monocytes were low and classical and plasmacytoid DCs were nearly absent. Counts of epidermal Langerhans cells and dermal macrophages in the skin were normal, but the patients lacked dermal DCs. These three adult patients suffered from various recurrent viral, bacterial, and fungal infections, including severe cutaneous warts in particular. They had nevertheless survived into adulthood despite an almost complete lack of blood and skin DCs. FLT3L is required for the development of B cells and DCs in both mice and humans. However, unlike its murine counterpart, human FLT3L is required for the development of monocytes, but not NK cells.

ORGANISM(S): Homo sapiens (human)

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PROVIDER: S-BSST1333 | biostudies-other |

REPOSITORIES: biostudies-other

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