title: Targeting dendritic cell function during systemic autoimmunity to restore tolerance.
abstract: Systemic autoimmune diseases can damage nearly every tissue or cell type of the body. Although a great deal of progress has been made in understanding the pathogenesis of autoimmune diseases, current therapies have not been improved, remain unspecific and are associated with significant side effects. Because dendritic cells (DCs) play a major role in promoting immune tolerance against self-antigens (self-Ags), current efforts are focusing at generating new therapies based on the transfer of tolerogenic DCs (tolDCs) during autoimmunity. However, the feasibility of this approach during systemic autoimmunity has yet to be evaluated. TolDCs may ameliorate autoimmunity mainly by restoring T cell tolerance and, thus, indirectly modulating autoantibody development. In vitro induction of tolDCs loaded with immunodominant self-Ags and subsequent cell transfer to patients would be a specific new therapy that will avoid systemic immunosuppression. Herein, we review recent approaches evaluating the potential of tolDCs for the treatment of systemic autoimmune disorders.
authors.affiliation: Millennium Institute of Immunology and Immunotherapy, Departamento de Genética Molecular y Microbiología, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Portugal 49, Santiago 8330025, Chile. jmackern@bio.puc.cl.
authors.forename: Juan P
authors.initials: JP
authors.lastname: Mackern-Oberti
authors.affiliation: Departamento de Inmunología Clínica y Reumatología, Escuela de Medicina, Pontificia Universidad Católica de Chile, Marcoleta 350, Santiago 8330033, Chile. fab.vega.t@gmail.com.
authors.forename: Fabián
authors.initials: F
authors.lastname: Vega
authors.affiliation: Departamento de Inmunología Clínica y Reumatología, Escuela de Medicina, Pontificia Universidad Católica de Chile, Marcoleta 350, Santiago 8330033, Chile. cllanosm@gmail.com.
authors.forename: Carolina
authors.initials: C
authors.lastname: Llanos
authors.affiliation: Millennium Institute of Immunology and Immunotherapy, Departamento de Genética Molecular y Microbiología, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Portugal 49, Santiago 8330025, Chile. sbueno@bio.puc.cl.
authors.forename: Susan M
authors.initials: SM
authors.lastname: Bueno
authors.affiliation: Millennium Institute of Immunology and Immunotherapy, Departamento de Genética Molecular y Microbiología, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Portugal 49, Santiago 8330025, Chile. akalergis@bio.puc.cl.
authors.forename: Alexis M
authors.initials: AM
authors.lastname: Kalergis
mesh_terms: D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use; D001327:Autoimmune Diseases / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D001402:B-Lymphocytes / Q000276:immunology; D002762:Cholecalciferol / Q000627:therapeutic use; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000627:therapeutic use; D006801:Humans; D007108:Immune Tolerance; D009570:Nitriles / Q000627:therapeutic use; D013450:Sulfones / Q000627:therapeutic use; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: C434003:3-(4-methylphenylsulfonyl)-2-propenenitrile; D000893:Anti-Inflammatory Agents; D009570:Nitriles; D013450:Sulfones; D002762:Cholecalciferol; D016178:Granulocyte-Macrophage Colony-Stimulating Factor