Distinct ontogenetic lineages dictate cDC2 heterogeneity

Distinct ontogenetic lineages dictate cDC2 heterogeneity

March 2024 | Carlos M. Minuti, Cécile 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
This study investigates the ontogenetic lineages that determine the heterogeneity of conventional dendritic cells (cDCs), specifically cDC2 subsets. The research reveals that cDC2s are not merely cell states determined by the peripheral tissue environment but are instead defined by distinct ontogenetic lineages. The study identifies two distinct pre-cDC2 subsets in the bone marrow: one that gives rise to cDC2As and another that gives rise to cDC2Bs. These subsets are characterized by their expression of Siglec-H and CD8α, respectively. The study further shows that the specification of cDC2A and cDC2B fates begins in the bone marrow and is influenced by signals such as Notch and lymphotoxin. The findings suggest that cDC2 subsets are determined by their developmental lineage rather than by environmental cues in peripheral tissues. The study also highlights the importance of the bone marrow in the specification of cDC2 lineages and demonstrates that the differentiation of cDC2As and cDC2Bs is influenced by signals present in the bone marrow. The research provides a framework for understanding the ontogeny of cDC2 subsets and their functional roles in immune responses.This study investigates the ontogenetic lineages that determine the heterogeneity of conventional dendritic cells (cDCs), specifically cDC2 subsets. The research reveals that cDC2s are not merely cell states determined by the peripheral tissue environment but are instead defined by distinct ontogenetic lineages. The study identifies two distinct pre-cDC2 subsets in the bone marrow: one that gives rise to cDC2As and another that gives rise to cDC2Bs. These subsets are characterized by their expression of Siglec-H and CD8α, respectively. The study further shows that the specification of cDC2A and cDC2B fates begins in the bone marrow and is influenced by signals such as Notch and lymphotoxin. The findings suggest that cDC2 subsets are determined by their developmental lineage rather than by environmental cues in peripheral tissues. The study also highlights the importance of the bone marrow in the specification of cDC2 lineages and demonstrates that the differentiation of cDC2As and cDC2Bs is influenced by signals present in the bone marrow. The research provides a framework for understanding the ontogeny of cDC2 subsets and their functional roles in immune responses.
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