Human Dendritic Cells (DCs) Are Derived from Distinct Circulating Precursors That Are Precommitted to Become CD1c+ or CD141+ DCs

Overview

Journal J Exp Med

Specialties Allergy & Immunology
General Medicine

Date 2016 Nov 20

PMID 27864467

Citations 61

Authors

Gaelle Breton

Shiwei Zheng

Renan Valieris

Israel Tojal Da Silva

Rahul Satija

Michel C Nussenzweig

Affiliations

Soon will be listed here.

Abstract

In humans, conventional dendritic cells (cDCs) exist as two unique populations characterized by expression of CD1c and CD141. cDCs arise from increasingly restricted but well-defined bone marrow progenitors that include the common DC progenitor that differentiates into the pre-cDC, which is the direct precursor of cDCs. In this study, we show that pre-cDCs in humans are heterogeneous, consisting of two distinct populations of precursors that are precommitted to become either CD1c or CD141 cDCs. The two groups of lineage-primed precursors can be distinguished based on differential expression of CD172a. Both subpopulations of pre-cDCs arise in the adult bone marrow and can be found in cord blood and adult peripheral blood. Gene expression analysis revealed that CD172a and CD172a pre-cDCs represent developmentally discrete populations that differentially express lineage-restricted transcription factors. A clinical trial of Flt3L injection revealed that this cytokine increases the number of both CD172a and CD172a pre-cDCs in human peripheral blood.

Citing Articles

Cross-priming in cancer immunology and immunotherapy.

Luri-Rey C, Teijeira A, Wculek S, de Andrea C, Herrero C, Lopez-Janeiro A Nat Rev Cancer. 2025; .

PMID: 39881005 DOI: 10.1038/s41568-024-00785-5.

Pre-pregnancy obesity is associated with an altered maternal metabolome and reduced Flt3L expression in preterm birth.

Sebina I, Bidgood C, Stalley F, Hartel G, Stark T, Callaway L Sci Rep. 2024; 14(1):30027.

PMID: 39627409 PMC: 11615298. DOI: 10.1038/s41598-024-81194-4.

Quantitative trait loci mapping provides insights into the genetic regulation of dendritic cell numbers in mouse tissues.

Oliveira T, Merkenschlager J, Eisenreich T, Bortolatto J, Yao K, Gatti D Cell Rep. 2024; 43(6):114296.

PMID: 38823019 PMC: 11726347. DOI: 10.1016/j.celrep.2024.114296.

Therapeutically targeting type I interferon directly to XCR1+ dendritic cells reveals the role of cDC1s in anti-drug antibodies.

Noe P, Wang J, Chung K, Cheng Z, Field J, Shen X Front Immunol. 2023; 14:1272055.

PMID: 37942313 PMC: 10628189. DOI: 10.3389/fimmu.2023.1272055.

Emerging Roles for Dendritic Cells in Heart Failure.

Saleh D, Jones R, Schroth S, Thorp E, Feinstein M Biomolecules. 2023; 13(10).

PMID: 37892217 PMC: 10605025. DOI: 10.3390/biom13101535.

References

Schlitzer A, Sivakamasundari V, Chen J, Sumatoh H, Schreuder J, Lum J . Identification of cDC1- and cDC2-committed DC progenitors reveals early lineage priming at the common DC progenitor stage in the bone marrow. Nat Immunol. 2015; 16(7):718-28. DOI: 10.1038/ni.3200. View

Schlitzer A, McGovern N, Teo P, Zelante T, Atarashi K, Low D . IRF4 transcription factor-dependent CD11b+ dendritic cells in human and mouse control mucosal IL-17 cytokine responses. Immunity. 2013; 38(5):970-83. PMC: 3666057. DOI: 10.1016/j.immuni.2013.04.011. View

Love M, Huber W, Anders S . Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol. 2014; 15(12):550. PMC: 4302049. DOI: 10.1186/s13059-014-0550-8. View

Jongbloed S, Kassianos A, McDonald K, Clark G, Ju X, Angel C . Human CD141+ (BDCA-3)+ dendritic cells (DCs) represent a unique myeloid DC subset that cross-presents necrotic cell antigens. J Exp Med. 2010; 207(6):1247-60. PMC: 2882828. DOI: 10.1084/jem.20092140. View

Steinman R, Hemmi H . Dendritic cells: translating innate to adaptive immunity. Curr Top Microbiol Immunol. 2006; 311:17-58. DOI: 10.1007/3-540-32636-7_2. View

Cohn L, Chatterjee B, Esselborn F, Smed-Sorensen A, Nakamura N, Chalouni C . Antigen delivery to early endosomes eliminates the superiority of human blood BDCA3+ dendritic cells at cross presentation. J Exp Med. 2013; 210(5):1049-63. PMC: 3646496. DOI: 10.1084/jem.20121251. View

Paul F, Arkin Y, Giladi A, Jaitin D, Kenigsberg E, Keren-Shaul H . Transcriptional Heterogeneity and Lineage Commitment in Myeloid Progenitors. Cell. 2015; 163(7):1663-77. DOI: 10.1016/j.cell.2015.11.013. View

Crozat K, Guiton R, Contreras V, Feuillet V, Dutertre C, Ventre E . The XC chemokine receptor 1 is a conserved selective marker of mammalian cells homologous to mouse CD8alpha+ dendritic cells. J Exp Med. 2010; 207(6):1283-92. PMC: 2882835. DOI: 10.1084/jem.20100223. View

Dobin A, Davis C, Schlesinger F, Drenkow J, Zaleski C, Jha S . STAR: ultrafast universal RNA-seq aligner. Bioinformatics. 2012; 29(1):15-21. PMC: 3530905. DOI: 10.1093/bioinformatics/bts635. View

10.

Notta F, Zandi S, Takayama N, Dobson S, Gan O, Wilson G . Distinct routes of lineage development reshape the human blood hierarchy across ontogeny. Science. 2015; 351(6269):aab2116. PMC: 4816201. DOI: 10.1126/science.aab2116. View

11.

Perie L, Duffy K, Kok L, De Boer R, Schumacher T . The Branching Point in Erythro-Myeloid Differentiation. Cell. 2015; 163(7):1655-62. DOI: 10.1016/j.cell.2015.11.059. View

12.

Steinman R, Banchereau J . Taking dendritic cells into medicine. Nature. 2007; 449(7161):419-26. DOI: 10.1038/nature06175. View

13.

Villadangos J, Shortman K . Found in translation: the human equivalent of mouse CD8+ dendritic cells. J Exp Med. 2010; 207(6):1131-4. PMC: 2882838. DOI: 10.1084/jem.20100985. View

14.

Robbins S, Walzer T, Dembele D, Thibault C, Defays A, Bessou G . Novel insights into the relationships between dendritic cell subsets in human and mouse revealed by genome-wide expression profiling. Genome Biol. 2008; 9(1):R17. PMC: 2395256. DOI: 10.1186/gb-2008-9-1-r17. View

15.

Satija R, Farrell J, Gennert D, Schier A, Regev A . Spatial reconstruction of single-cell gene expression data. Nat Biotechnol. 2015; 33(5):495-502. PMC: 4430369. DOI: 10.1038/nbt.3192. View

16.

Breton G, Lee J, Liu K, Nussenzweig M . Defining human dendritic cell progenitors by multiparametric flow cytometry. Nat Protoc. 2015; 10(9):1407-22. PMC: 4607256. DOI: 10.1038/nprot.2015.092. View

17.

Anders S, Pyl P, Huber W . HTSeq--a Python framework to work with high-throughput sequencing data. Bioinformatics. 2014; 31(2):166-9. PMC: 4287950. DOI: 10.1093/bioinformatics/btu638. View

18.

Macosko E, Basu A, Satija R, Nemesh J, Shekhar K, Goldman M . Highly Parallel Genome-wide Expression Profiling of Individual Cells Using Nanoliter Droplets. Cell. 2015; 161(5):1202-1214. PMC: 4481139. DOI: 10.1016/j.cell.2015.05.002. View

19.

Shalek A, Satija R, Shuga J, Trombetta J, Gennert D, Lu D . Single-cell RNA-seq reveals dynamic paracrine control of cellular variation. Nature. 2014; 510(7505):363-9. PMC: 4193940. DOI: 10.1038/nature13437. View

20.

Efroni I, Mello A, Nawy T, Ip P, Rahni R, DelRose N . Root Regeneration Triggers an Embryo-like Sequence Guided by Hormonal Interactions. Cell. 2016; 165(7):1721-1733. PMC: 4912400. DOI: 10.1016/j.cell.2016.04.046. View