title: Transcriptional reprogramming of CD11b+Esam(hi) dendritic cell identity and function by loss of Runx3.
abstract: Classical dendritic cells (cDC) are specialized antigen-presenting cells mediating immunity and tolerance. cDC cell-lineage decisions are largely controlled by transcriptional factor regulatory cascades. Using an in vivo cell-specific targeting of Runx3 at various stages of DC lineage development we show that Runx3 is required for cell-identity, homeostasis and function of splenic Esam(hi) DC. Ablation of Runx3 in DC progenitors led to a substantial decrease in splenic CD4(+)/CD11b(+) DC. Combined chromatin immunoprecipitation sequencing and gene expression analysis of purified DC-subsets revealed that Runx3 is a key gene expression regulator that facilitates specification and homeostasis of CD11b(+)Esam(hi) DC. Mechanistically, loss of Runx3 alters Esam(hi) DC gene expression to a signature characteristic of WT Esam(low) DC. This transcriptional reprogramming caused a cellular change that diminished phagocytosis and hampered Runx3(-/-) Esam(hi) DC capacity to prime CD4(+) T cells, attesting to the significant role of Runx3 in specifying Esam(hi) DC identity and function.
authors.affiliation: Department of Molecular Genetics, The Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Joseph
authors.initials: J
authors.lastname: Dicken
authors.forename: Alexander
authors.initials: A
authors.lastname: Mildner
authors.forename: Dena
authors.initials: D
authors.lastname: Leshkowitz
authors.forename: Ivo P
authors.initials: IP
authors.lastname: Touw
authors.forename: Shay
authors.initials: S
authors.lastname: Hantisteanu
authors.forename: Steffen
authors.initials: S
authors.lastname: Jung
authors.forename: Yoram
authors.initials: Y
authors.lastname: Groner
mesh_terms: D000818:Animals; D039481:CD11b Antigen / Q000235:genetics* / Q000276:immunology; D015704:CD4 Antigens / Q000235:genetics / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000235:genetics* / Q000276:immunology; D002450:Cell Communication; D002454:Cell Differentiation; D019070:Cell Lineage / Q000276:immunology; D065150:Cellular Reprogramming / Q000235:genetics* / Q000276:immunology; D050677:Core Binding Factor Alpha 3 Subunit / Q000172:deficiency / Q000235:genetics* / Q000276:immunology; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D047468:Immunoprecipitation; D051379:Mice; D008822:Mice, Transgenic; D010587:Phagocytosis; D017422:Sequence Analysis, DNA; D015398:Signal Transduction; D013154:Spleen / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: D039481:CD11b Antigen; D015704:CD4 Antigens; D015815:Cell Adhesion Molecules; D050677:Core Binding Factor Alpha 3 Subunit; C428190:Esam protein, mouse; C493730:Runx3 protein, mouse