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© Research
Publication : Cell

FLT3L governs the development of partially overlapping hematopoietic lineages in humans and mice.

Team: Pathogen discovery
Member: Philippe Pérot
Scientific Fields
Diseases
Organisms
Applications
Technique

Published in Cell - 23 May 2024

Momenilandi M, Lévy R, Sobrino S, Li J, Lagresle-Peyrou C, Esmaeilzadeh H, Fayand A, Le Floc'h C, Guérin A, Mina ED, Shearer D, Delmonte OM, Yatim A, Mulder K, Mancini M, Rinchai D, Denis A, Neehus AL, Balogh K, Brendle S, Rokni-Zadeh H, Changi-Ashtiani M, Seeleuthner Y, Deswarte C, Bessot B, Cremades C, Materna M, Cederholm A, Ogishi M, Philippot Q, Beganovic O, Ackermann M, Wuyts M, Khan T, Fouéré S, Herms F, Chanal J, Palterer B, Bruneau J, Molina TJ, Leclerc-Mercier S, Prétet JL, Youssefian L, Vahidnezhad H, Parvaneh N, Claeys KG, Schrijvers R, Luka M, Pérot P, Fourgeaud J, Nourrisson C, Poirier P, Jouanguy E, Boisson-Dupuis S, Bustamante J, Notarangelo LD, Christensen N, Landegren N, Abel L, Marr N, Six E, Langlais D, Waterboer T, Ginhoux F, Ma CS, Tangye SG, Meyts I, Lachmann N, Hu J, Shahrooei M, Bossuyt X, Casanova JL, Béziat V

Link to Pubmed [PMID] – 38701783

Link to DOI – 10.1016/j.cell.2024.04.009

Cell 2024 May; 187(11): 2817-2837.e31

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 cell and DC development in mice and humans. However, unlike its murine counterpart, human FLT3L is required for the development of monocytes but not NK cells.