Id2 expression delineates differential checkpoints in the genetic program of CD8α+ and CD103+ dendritic cell lineages.
Jacob T. Jackson,Yifang Hu,Ruijie Liu,Frederick Masson,Angela D'Amico,Sebastian Carotta,Annie Xin,Annie Xin,Mary J Camilleri,Adele M. Mount,Axel Kallies,Axel Kallies,Li Wu,Li Wu,Gordon K. Smyth,Gordon K. Smyth,Stephen L. Nutt,Stephen L. Nutt,Gabrielle T. Belz,Gabrielle T. Belz +19 more
Reads0
Chats0
TLDR
It is shown that Id2 is broadly expressed in all cDC subsets with the highest expression in CD103+ and CD8α+ lineages and that Irf‐8 and Batf3 regulate distinct stages in DC differentiation during the development of cDCs.Abstract:
Dendritic cells (DCs) have critical roles in the induction of the adaptive immune response. The transcription factors Id2, Batf3 and Irf-8 are required for many aspects of murine DC differentiation including development of CD8α+ and CD103+ DCs. How they regulate DC subset specification is not completely understood. Using an Id2-GFP reporter system, we show that Id2 is broadly expressed in all cDC subsets with the highest expression in CD103+ and CD8α+ lineages. Notably, CD103+ DCs were the only DC able to constitutively cross-present cell-associated antigens in vitro. Irf-8 deficiency affected loss of development of virtually all conventional DCs (cDCs) while Batf3 deficiency resulted in the development of Sirp-α− DCs that had impaired survival. Exposure to GM-CSF during differentiation induced expression of CD103 in Id2-GFP+ DCs. It did not restore cross-presenting capacity to Batf3−/− or CD103−Sirp-α−DCs in vitro. Thus, Irf-8 and Batf3 regulate distinct stages in DC differentiation during the development of cDCs. Genetic mapping DC subset differentiation using Id2-GFP may have broad implications in understanding the interplay of DC subsets during protective and pathological immune responses.read more
Citations
More filters
Journal ArticleDOI
Id2 and E Proteins Orchestrate the Initiation and Maintenance of MLL-Rearranged Acute Myeloid Leukemia
Margherita Ghisi,Margherita Ghisi,Lev Kats,Lev Kats,Frederick Masson,Frederick Masson,Frederick Masson,Jason Li,Jason Li,Tobias Kratina,Tobias Kratina,Eva Vidacs,Omer Gilan,Omer Gilan,Maria A. Doyle,Andrea Newbold,Andrea Newbold,Jessica E. Bolden,Jessica E. Bolden,Kirsten A. Fairfax,Kirsten A. Fairfax,Carolyn A. de Graaf,Carolyn A. de Graaf,Matthew A. Firth,Matthew A. Firth,Johannes Zuber,Ross A. Dickins,Lynn M. Corcoran,Lynn M. Corcoran,Mark A. Dawson,Mark A. Dawson,Gabrielle T. Belz,Gabrielle T. Belz,Ricky W. Johnstone,Ricky W. Johnstone +34 more
TL;DR: It is found that Id2 acts as a key regulator of leukemia stem cell potential in MLL-rearranged acute myeloid leukemia (AML) and t(8;21) AML patients, identifying the Id2/E-protein axis as a promising new therapeutic target in AML.
Journal ArticleDOI
The Closely Related CD103+ Dendritic Cells (DCs) and Lymphoid-Resident CD8+ DCs Differ in Their Inflammatory Functions
Zhijun Jiao,Sammy Bedoui,Jamie L. Brady,Anne Walter,Michael Chopin,Emma M. Carrington,Robyn M. Sutherland,Stephen L. Nutt,Yuxia Zhang,Hyun-Ja Ko,Li Wu,Andrew M. Lew,Yifan Zhan +12 more
TL;DR: It is found that upon skin infection with herpes simplex virus, migratory CD103+ DCs from draining lymph nodes were more potent at inducing Th17 cytokine production by CD4+ T cells than CD8+DCs and that GM-CSF has differential effect on the two types of DCs.
Journal ArticleDOI
Dendritic Cell Development: A Choose-Your-Own-Adventure Story
TL;DR: How the combinatorial expression of transcription factors can promote one DC lineage over another as well as the integration of cytokine signaling in this process are discussed.
Journal ArticleDOI
Transcriptional Regulation of Dendritic Cell Diversity
TL;DR: The determinants that underpin cellular and transcriptional heterogeneity within the DC network are explored, how these influence DC distribution and localization at steady-state, and the capacity of DCs to present antigens via direct or cross-presentation during pathogen infection is explored.
Book ChapterDOI
Origin and development of classical dendritic cells.
Pierre Guermonprez,Pierre Guermonprez,Yohan Gerber-Ferder,Kristine Vaivode,Pierre Bourdely,Julie Helft,Julie Helft +6 more
TL;DR: Recent knowledge on the cellular and molecular pathways controlling the specification and commitment of cDC subsets from murine and human hematopoietic stem cells are presented.
References
More filters
Journal ArticleDOI
Development of Monocytes, Macrophages, and Dendritic Cells
TL;DR: The current understanding of myeloid lineage development is reviewed and the developmental pathways and cues that drive differentiation are described, which are central to the development of immunologic memory and tolerance in mice.
Journal ArticleDOI
T cell receptor antagonist peptides induce positive selection
Kristin A. Hogquist,Stephen C. Jameson,William R. Heath,Jane L Howard,Michael J. Bevan,Francis R. Carbone +5 more
TL;DR: Results show that the process of positive selection is exquisitely peptide specific and sensitive to extremely low ligand density and support the notion that low efficacy ligands mediate positive selection.
Journal ArticleDOI
Batf3 Deficiency Reveals a Critical Role for CD8α+ Dendritic Cells in Cytotoxic T Cell Immunity
Kai Hildner,Brian T. Edelson,Whitney E. Purtha,Mark S Diamond,Hirokazu Matsushita,Masako Kohyama,Boris Calderon,Barbara U. Schraml,Emil R. Unanue,Michael S. Diamond,Robert D. Schreiber,Theresa L. Murphy,Kenneth M. Murphy +12 more
TL;DR: An important role is suggested for CD8α+ dendritic cells and cross-presentation in responses to viruses and in tumor rejection in Batf3–/– mice.
Journal ArticleDOI
Defective TCR expression in transgenic mice constructed using cDNA-based alpha- and beta-chain genes under the control of heterologous regulatory elements
TL;DR: Results show that successful generation of MHC class II‐restricted, OVA‐specific αβTCR transgenic mice was dependent upon combining cDNA‐ and genomic DNA‐based constructs for expression of the respective α‐ and β‐chains of the TCR.
Journal ArticleDOI
BDCA-2, BDCA-3, and BDCA-4: Three Markers for Distinct Subsets of Dendritic Cells in Human Peripheral Blood
Andrzej Dzionek,Anja Fuchs,Petra Schmidt,Sabine Cremer,Monika Zysk,Stefan Miltenyi,David William Buck,Jürgen Schmitz +7 more
TL;DR: The three presumably novel Ags serve as specific markers for the respective subpopulations of blood dendritic cells in fresh blood and will be of great value for their further analysis and to evaluate their therapeutic potential.