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Conventional dendritic cells (cDC) are key activators of naive T cells, and can be targeted in adults to induce adaptive immunity, but in early life are considered under-developed or functionally immature. Here we show that, in early life, when the immune system develops, cDC2 exhibit a dual hematopoietic origin and, like other myeloid and lymphoid cells, develop in waves. Developmentally distinct cDC2 in early life, despite being distinguishable by fate mapping, are transcriptionally and functionally similar. cDC2 in early and adult life, however, are exposed to distinct cytokine environments that shape their transcriptional profile and alter their ability to sense pathogens, secrete cytokines and polarize T cells. We further show that cDC2 in early life, despite being distinct from cDC2 in adult life, are functionally competent and can induce T cell responses. Our results thus highlight the potential of harnessing cDC2 for boosting immunity in early life.

Original publication

DOI

10.1038/s41467-020-20659-2

Type

Journal article

Journal

Nat Commun

Publication Date

19/01/2021

Volume

12

Keywords

Adaptive Immunity, Age Factors, Animals, Cell Differentiation, Cell Separation, Cytokines, Dendritic Cells, Female, Flow Cytometry, Gene Expression Regulation, Developmental, Hematopoietic Stem Cells, Male, Mice, Mice, Transgenic, Models, Animal, Primary Cell Culture, RNA-Seq, Single-Cell Analysis, T-Lymphocytes, Transcriptome