Mechanisms regulating dendritic cell specification and development

• Published in: Immunological reviews Vol. 238; no. 1; pp. 76 - 92
• Main Authors: Watowich, Stephanie S, Liu, Yong‐Jun
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.11.2010
• Subjects: Animals; Cell Differentiation; Cell Lineage; Cytokines; Dendritic cells; Dendritic Cells - immunology; Development; Flt3 protein; FLT3L protein; Gene Expression Regulation, Developmental - immunology; Granulocyte-macrophage colony-stimulating factor; Granulocyte-Macrophage Colony-Stimulating Factor - immunology; hematopoiesis; Hematopoietic Stem Cells - immunology; Hemopoiesis; Humans; Immune System - embryology; Immune System - growth & development; Interferon; Interferon Type I - immunology; Learning; lineage commitment/specification; Mapping; Membrane Proteins - immunology; Signal transduction; Signal Transduction - immunology; Stem cells; Transcription factors
• ISSN: 0105-2896; 1600-065X
• DOI: 10.1111/j.1600-065X.2010.00949.x

Understanding the diversification of dendritic cell (DC) lineages is one of the last frontiers in mapping the developmental hierarchy of the hematopoietic system. DCs are a vital link between the innate and adaptive immune responses; thus, elucidating their developmental pathways is crucial for insight into the generation of natural immunity and for learning how to regulate DCs in clinical settings. DCs arise from hematopoietic stem cells through specialized progenitor subsets under the direction of FMS‐like tyrosine kinase 3 ligand (Flt3L) and Flt3L receptor (Flt3) signaling. Recent studies have revealed important contributions from granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) and type I interferons (IFNs) in vivo. Furthermore, DC development is guided by lineage‐restricted transcription factors such as IRF8, E2‐2, and Batf3. A critical question centers on how cytokines and lineage‐restricted transcription factors operate molecularly to direct DC diversification. Here, we review recent findings that provide new insight into the DC developmental process.