title: Molecular programming of steady-state dendritic cells: impact on autoimmunity and tumor immune surveillance.
abstract: Dendritic cells are master regulators of immunity. Immature dendritic cells are essential for maintaining self-tolerance, while mature dendritic cells initiate a variety of specialized immune responses. Dendritic cell quiescence is often viewed as a default state that requires exogenous stimuli to induce maturation. However, recent studies have identified dendritic cell quiescence factors that actively program dendritic cells to an immature state. In the absence of these factors, dendritic cells spontaneously become immunogenic and can induce autoimmune responses. Herein we discuss two such factors, NF-κB1 and A20, that preserve dendritic cell immaturity through their regulation of NF-κB signaling. Loss of either of these factors increases dendritic cell immunogenicity, suggesting that they may be important targets for enhancing dendritic cell-based cancer immunotherapies. Alternatively, defects in molecules critical for maintaining steady-state DCs may provide novel biomarkers that identify patients who have enhanced natural antitumor immunity or that correlate with better responses to various immunotherapies.
authors: Campbell Family Institute for Breast Cancer Research, Princess Margaret Cancer Center, University Health Network, Toronto, Ontario, Canada.
authors: Dylan J
authors: DJ
authors: Johnson
authors: Pamela S
authors: PS
authors: Ohashi
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D000941:Antigens / Q000378:metabolism; D001324:Autoantigens / Q000276:immunology; D015551:Autoimmunity; D003713:Dendritic Cells / Q000276:immunology*; D006706:Homeostasis; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology; D007157:Immunologic Surveillance / Q000276:immunology*; D016328:NF-kappa B / Q000378:metabolism; D009369:Neoplasms / Q000276:immunology*; D017634:Self Tolerance / Q000276:immunology; D015398:Signal Transduction
chemical_list: D000941:Antigens; D001324:Autoantigens; D016328:NF-kappa B