Journal
JOURNAL OF IMMUNOLOGY
Volume 205, Issue 8, Pages 2117-2127Publisher
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.2000742
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Funding
- Natural Sciences and Engineering Research Council of Canada [2014-06531, 2019-05047]
- Lucie Besner Foundation
- Montreal Diabetes Research Center
- Departement de Microbiologie, Infectiologie et Immunologie at the Universite de Montreal
- Fonds de Recherche Quebec Sante
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Conventional dendritic cells (cDCs) are comprised of two major subsets, type 1 cDC (cDC1) and type 2 cDC (cDC2). As each cDC subset differentially influences the nature of immune responses, we sought factors that would allow the manipulation of their relative abundance. Notably, cDC1 are less abundant than cDC2 in both lymphoid and nonlymphoid organs. We demonstrate that this bias is already apparent in bone marrow precommitted precursors. However, comparison of five common inbred strains revealed a disparity in precursor-product relationship, in which mice with fewer precursors to cDC1 had more cDC1. This disparity associated with contrasting variations in CD135 (FLT3) expression on cDC subsets. Hence, we characterized the response to FLT3 ligand during cDC1 and cDC2 lineage differentiation and find that although FLT3 ligand is required throughout cDC2 differentiation, it is surprisingly dispensable during late-stage cDC1 differentiation. Overall, we find that tight regulation of FLT3 ligand levels throughout cDC differentiation dictates the cDC1 to cDC2 ratio in lymphoid organs.
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