title: Plasmacytoid dendritic cells activate lymphoid-specific genetic programs irrespective of their cellular origin.
abstract: The developmental origin of type I interferon (IFN)-producing plasmacytoid dendritic cells (PDCs) is controversial. In particular, the rearrangement of immunoglobulin heavy chain (IgH) genes in murine PDCs and the expression of pre-T cell receptor alpha (pTalpha) gene by human PDCs were proposed as evidence for their "lymphoid" origin. Here we demonstrate that PDCs capable of IFN production develop efficiently from both myeloid- and lymphoid-committed progenitors. Rearranged IgH genes as well as RAG transcripts were found in both myeloid- and lymphoid-derived PDCs. The human pTalpha transgenic reporter was activated in both myeloid- and lymphoid-derived PDCs at a level comparable to pre-T cells. PDCs were the only cell population that activated murine RAG1 knockin and human pTalpha transgenic reporters outside the lymphoid lineage. These results highlight a unique developmental program of PDCs that distinguishes them from other cell types including conventional dendritic cells.
authors.affiliation: Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Shigematsu
authors.forename: Boris
authors.initials: B
authors.lastname: Reizis
authors.forename: Hiromi
authors.initials: H
authors.lastname: Iwasaki
authors.forename: Shin-ichi
authors.initials: S
authors.lastname: Mizuno
authors.forename: Dan
authors.initials: D
authors.lastname: Hu
authors.forename: David
authors.initials: D
authors.lastname: Traver
authors.forename: Philip
authors.initials: P
authors.lastname: Leder
authors.forename: Nobuo
authors.initials: N
authors.lastname: Sakaguchi
authors.forename: Koichi
authors.initials: K
authors.lastname: Akashi
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000502:physiology*; D002454:Cell Differentiation; D019070:Cell Lineage; D003713:Dendritic Cells / Q000502:physiology*; D015326:Gene Rearrangement, B-Lymphocyte, Heavy Chain; D006412:Hematopoietic Stem Cells / Q000502:physiology*; D018398:Homeodomain Proteins / Q000378:metabolism; D006801:Humans; D007370:Interferon Type I / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D010950:Plasma Cells / Q000502:physiology*; D016693:Receptors, Antigen, T-Cell, alpha-beta
chemical_list: D018398:Homeodomain Proteins; D007370:Interferon Type I; D008562:Membrane Glycoproteins; D016693:Receptors, Antigen, T-Cell, alpha-beta; C090377:pre-T cell receptor alpha; C064658:RAG-1 protein