title: Novel immunoregulatory role of perforin-positive dendritic cells.
abstract: The recently described generation of a highly defined population of dendritic cells which express perforin and granzyme A (termed "perf-DCs") and their ability to selectively delete cognate CD8+ T cell has raised the possibility that these cells play a role in the maintenance of peripheral tolerance. Using bone marrow transplantation, we generated mice selectively lacking perforin expressing dendritic cells. These mice progressively gain weight and exhibit features resembling metabolic syndrome as well as an enhanced susceptibility to autoimmunity induction. Interestingly, these pathological phenotypes were reversed upon treatment with CD4/CD8 neutralizing antibodies. Thus, it appears that this rare subpopulation of dendritic cells (perf-DCs) displays a major regulatory role in adipose tissue inflammatory processes and in autoimmunity.
authors: Department of Immunology, Weizmann Institute of Science, Herzel St. 1, 76100, Rehovot, Israel.
authors: Ran
authors: R
authors: Orgad
authors: Department of Immunology, Weizmann Institute of Science, Herzel St. 1, 76100, Rehovot, Israel.
authors: Bar
authors: B
authors: Nathansohn-Levi
authors: Department of Immunology, Weizmann Institute of Science, Herzel St. 1, 76100, Rehovot, Israel.
authors: Sivan
authors: S
authors: Kagan
authors: Department of Immunology, Weizmann Institute of Science, Herzel St. 1, 76100, Rehovot, Israel.
authors: Yael
authors: Y
authors: Zlotnikov Klionsky
authors: Department of Immunology, Weizmann Institute of Science, Herzel St. 1, 76100, Rehovot, Israel. yair.reisner@weizmann.ac.il.
authors: Yair
authors: Y
authors: Reisner
mesh_terms: D000818:Animals; D015551:Autoimmunity; D002454:Cell Differentiation; D003602:Cytotoxicity, Immunologic; D003713:Dendritic Cells / Q000145:classification / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D004195:Disease Models, Animal; D004198:Disease Susceptibility; D004681:Encephalomyelitis, Autoimmune, Experimental; D006649:Histocompatibility Antigens / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007108:Immune Tolerance; D056747:Immunomodulation; D024821:Metabolic Syndrome / Q000209:etiology / Q000378:metabolism; D054353:Perforin / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism
chemical_list: D006649:Histocompatibility Antigens; D054353:Perforin
keywords: Autoimmunity; Dendritic cells; Metabolic syndrome; Perforin