Distinct ontogenetic lineages dictate cDC2 heterogeneity.

Autor: Minutti CM; Immunobiology Laboratory, The Francis Crick Institute, London, UK. carlos.minutti@research.fchampalimaud.org.; Immunoregulation Laboratory, Champalimaud Research, Champalimaud Centre for the Unknown, Lisbon, Portugal. carlos.minutti@research.fchampalimaud.org., Piot C; Immunobiology Laboratory, The Francis Crick Institute, London, UK., Pereira da Costa M; Immunobiology Laboratory, The Francis Crick Institute, London, UK., Chakravarty P; Bioinformatics and Biostatistics, The Francis Crick Institute, London, UK., Rogers N; Immunobiology Laboratory, The Francis Crick Institute, London, UK., Huerga Encabo H; Haematopoietic Stem Cell Laboratory, The Francis Crick Institute, London, UK., Cardoso A; Immunobiology Laboratory, The Francis Crick Institute, London, UK., Loong J; Retroviral Immunology Laboratory, The Francis Crick Institute, London, UK., Bessou G; Aix-Marseille University, Centre National de la Recherche Scientifique, Institut National de la Santé et de la Recherche Médicale, Centre d'Immunologie de Marseille-Luminy, Turing Center for Living Systems, Marseille, France., Mionnet C; Aix-Marseille University, Centre National de la Recherche Scientifique, Institut National de la Santé et de la Recherche Médicale, Centre d'Immunologie de Marseille-Luminy, Turing Center for Living Systems, Marseille, France., Langhorne J; Malaria Immunology Laboratory, The Francis Crick Institute, London, UK., Bonnet D; Haematopoietic Stem Cell Laboratory, The Francis Crick Institute, London, UK., Dalod M; Aix-Marseille University, Centre National de la Recherche Scientifique, Institut National de la Santé et de la Recherche Médicale, Centre d'Immunologie de Marseille-Luminy, Turing Center for Living Systems, Marseille, France., Tomasello E; Aix-Marseille University, Centre National de la Recherche Scientifique, Institut National de la Santé et de la Recherche Médicale, Centre d'Immunologie de Marseille-Luminy, Turing Center for Living Systems, Marseille, France., Reis E Sousa C; Immunobiology Laboratory, The Francis Crick Institute, London, UK. caetano@crick.ac.uk.
Jazyk: angličtina
Zdroj: Nature immunology [Nat Immunol] 2024 Mar; Vol. 25 (3), pp. 448-461. Date of Electronic Publication: 2024 Feb 13.
DOI: 10.1038/s41590-024-01745-9
Abstrakt: 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.
(© 2024. The Author(s).)
Databáze: MEDLINE
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