title: The origin of DCs and capacity for immunologic tolerance in central and peripheral tissues.
abstract: Dendritic cells (DCs) are specialized immune sentinels that play key role in maintaining immune homeostasis by efficiently regulating the delicate balance between protective immunity and tolerance to self. Although DCs respond to maturation signals present in the surrounding milieu, multiple layers of suppression also co-exist that reduce the infringement of tolerance against self-antigens. These tolerance inducing properties of DCs are governed by their origin and a range of other factors including distribution, cytokines, growth factors, and transcriptional programing, that collectively impart suppressive functions to these cells. DCs directing tolerance secrete anti-inflammatory cytokines and induce naïve T cells or B cells to differentiate into regulatory T cells (Tregs) or B cells. In this review, we provide a detailed outlook on the molecular mechanisms that induce functional specialization to govern central or peripheral tolerance. The tolerance-inducing nature of DCs can be exploited to overcome autoimmunity and rejection in graft transplantation.
authors.affiliation: Department of Dermatology/Harvard Skin Disease Research Center, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: K Sanjana P
authors.initials: KS
authors.lastname: Devi
authors.affiliation: Department of Dermatology/Harvard Skin Disease Research Center, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. Nanandasabapathy@partners.org.
authors.forename: Niroshana
authors.initials: N
authors.lastname: Anandasabapathy
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D060151:B-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism; D002454:Cell Differentiation; D045142:Cross-Priming / Q000276:immunology; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000145:classification / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D005786:Gene Expression Regulation; D016298:Hematopoietic Cell Growth Factors / Q000378:metabolism; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism; D006706:Homeostasis; D006801:Humans; D007108:Immune Tolerance; D056747:Immunomodulation; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D009928:Organ Specificity / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic; D014612:Vaccines / Q000276:immunology
chemical_list: D016207:Cytokines; D016298:Hematopoietic Cell Growth Factors; D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D014157:Transcription Factors; D014612:Vaccines; C084881:flt3 ligand protein
keywords: Tolerogenic DCs; cytokines; growth factors; immune homeostasis; regulatory T cells; transcription factors