Distinct Ontogenetic Lineages Dictate CDC2 Heterogeneity

Overview

Journal Nat Immunol

Date 2024 Feb 13

PMID 38351322

Authors

Carlos M Minutti

Cecile Piot

Mariana Pereira da Costa

Probir Chakravarty

Neil Rogers

Hector Huerga Encabo

Ana Cardoso

Jane Loong

Gilles Bessou

Cyrille Mionnet

Jean Langhorne

Dominique Bonnet

Marc Dalod

Elena Tomasello

Caetano Reis e Sousa

Affiliations

Soon will be listed here.

Abstract

Conventional dendritic cells (cDCs) include functionally and phenotypically diverse populations, such as cDC1s and cDC2s. The latter population has been variously subdivided into Notch-dependent cDC2s, KLF4-dependent cDC2s, T-bet cDC2As and T-bet cDC2Bs, but it is unclear how all these subtypes are interrelated and to what degree they represent cell states or cell subsets. All cDCs are derived from bone marrow progenitors called pre-cDCs, which circulate through the blood to colonize peripheral tissues. Here, we identified distinct mouse pre-cDC2 subsets biased to give rise to cDC2As or cDC2Bs. We showed that a Siglec-H pre-cDC2A population in the bone marrow preferentially gave rise to Siglec-H CD8α pre-cDC2As in tissues, which differentiated into T-bet cDC2As. In contrast, a Siglec-H fraction of pre-cDCs in the bone marrow and periphery mostly generated T-bet cDC2Bs, a lineage marked by the expression of LysM. Our results showed that cDC2A versus cDC2B fate specification starts in the bone marrow and suggest that cDC2 subsets are ontogenetically determined lineages, rather than cell states imposed by the peripheral tissue environment.

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