biostudies-literatureMomenilandi MNIDCR NIH HHSNCATS NIH HHSEuropean Research CouncilHoward Hughes Medical InstituteNIAID NIH HHSLEO FoundationNCI NIH HHS2817-2837.e31https://www.ebi.ac.uk/biostudies/studies/S-EPMC11149630biostudies-literatureUnknown187(11)FMS-related tyrosine kinase 3 ligand (FLT3L), encoded by FLT3LG, is a hematopoietic factor essential for the development of natural killer (NK) cells, B cells, and dendritic cells (DCs) in mice. We describe three humans homozygous for a loss-of-function FLT3LG variant with a history of various recurrent infections, including severe cutaneous warts. The patients' bone marrow (BM) was hypoplastic, with low levels of hematopoietic progenitors, particularly myeloid and B cell precursors. Counts of B cells, monocytes, and DCs were low in the patients' blood, whereas the other blood subsets, including NK cells, were affected only moderately, if at all. The patients had normal counts of Langerhans cells (LCs) and dermal macrophages in the skin but lacked dermal DCs. Thus, FLT3L is required for B CellFLT3L governs the development of partially overlapping hematopoietic lineages in humans and mice.PMC11149630LF-OC-22-000965R21 DE028650R01 AI143810R21 CA271069UL1 TR001866R21 AI121822948959R21 CA274265Materna MBossuyt XPoirier PFouere SClaeys KGBalogh KSchrijvers RPerot PPretet JLLandegren NParvaneh NNourrisson CLi JLanglais DSix EEsmaeilzadeh HMomenilandi MSobrino SFayand AShearer DNotarangelo LDAbel LCasanova JLPhilippot QAckermann MGinhoux FYatim AMa CSHu JMulder KYoussefian LLevy RDeswarte CGuerin ABustamante JChanal JOgishi MFourgeaud JChristensen NCederholm AVahidnezhad HSeeleuthner YBruneau JNeehus ALBeganovic OMeyts IHerms FMarr NRokni-Zadeh HPalterer BJouanguy EWaterboer TDelmonte OMLachmann NChangi-Ashtiani MLeclerc-Mercier SBessot BRinchai DWuyts MMolina TJShahrooei MDella Mina ETangye SGCremades CBoisson-Dupuis SLe Floc'h CMancini MDenis AKhan TBeziat VLagresle-Peyrou CBrendle SLuka MfalseFLT3L governs the development of partially overlapping hematopoietic lineages in humans and mice.FMS-related tyrosine kinase 3 ligand (FLT3L), encoded by FLT3LG, is a hematopoietic factor essential for the development of natural killer (NK) cells, B cells, and dendritic cells (DCs) in mice. We describe three humans homozygous for a loss-of-function FLT3LG variant with a history of various recurrent infections, including severe cutaneous warts. The patients' bone marrow (BM) was hypoplastic, with low levels of hematopoietic progenitors, particularly myeloid and B cell precursors. Counts of B cells, monocytes, and DCs were low in the patients' blood, whereas the other blood subsets, including NK cells, were affected only moderately, if at all. The patients had normal counts of Langerhans cells (LCs) and dermal macrophages in the skin but lacked dermal DCs. Thus, FLT3L is required for B 2024-01-01T00:00:00Z2024 May2026-04-24T03:19:02.562Z2026-04-24T03:09:53.858ZS-EPMC111496303870178310.1016/j.cell.2024.04.009