title: Perforin-Positive Dendritic Cells Exhibit an Immuno-regulatory Role in Metabolic Syndrome and Autoimmunity.
abstract: Emerging evidence suggests that immunological mechanisms underlie metabolic control of adipose tissue. Here, we have shown the regulatory impact of a rare subpopulation of dendritic cells, rich in perforin-containing granules (perf-DCs). Using bone marrow transplantation to generate animals selectively lacking perf-DCs, we found that these chimeras progressively gained weight and exhibited features of metabolic syndrome. This phenotype was associated with an altered repertoire of T cells residing in adipose tissue and could be completely prevented by T cell depletion in vivo. A similar impact of perf-DCs on inflammatory T cells was also found in a well-defined model of multiple sclerosis, experimental autoimmune encephlalomyelitis (EAE). Thus, perf-DCs probably represent a regulatory cell subpopulation critical for protection from metabolic syndrome and autoimmunity.
authors.affiliation: Department of Immunology, Weizmann Institute of Science, Herzel St 1, Rehovot 76100, Israel.
authors.forename: Yael
authors.initials: Y
authors.lastname: Zlotnikov-Klionsky
authors.affiliation: Department of Immunology, Weizmann Institute of Science, Herzel St 1, Rehovot 76100, Israel.
authors.forename: Bar
authors.initials: B
authors.lastname: Nathansohn-Levi
authors.affiliation: Department of Immunology, Weizmann Institute of Science, Herzel St 1, Rehovot 76100, Israel.
authors.forename: Elias
authors.initials: E
authors.lastname: Shezen
authors.affiliation: Department of Immunology, Weizmann Institute of Science, Herzel St 1, Rehovot 76100, Israel.
authors.forename: Chava
authors.initials: C
authors.lastname: Rosen
authors.affiliation: Department of Immunology, Weizmann Institute of Science, Herzel St 1, Rehovot 76100, Israel.
authors.forename: Sivan
authors.initials: S
authors.lastname: Kagan
authors.affiliation: Department of Immunology, Weizmann Institute of Science, Herzel St 1, Rehovot 76100, Israel.
authors.forename: Liat
authors.initials: L
authors.lastname: Bar-On
authors.affiliation: Department of Immunology, Weizmann Institute of Science, Herzel St 1, Rehovot 76100, Israel.
authors.forename: Steffen
authors.initials: S
authors.lastname: Jung
authors.affiliation: Department of Immunology, Weizmann Institute of Science, Herzel St 1, Rehovot 76100, Israel.
authors.forename: Eric
authors.initials: E
authors.lastname: Shifrut
authors.affiliation: Department of Immunology, Weizmann Institute of Science, Herzel St 1, Rehovot 76100, Israel.
authors.forename: Shlomit
authors.initials: S
authors.lastname: Reich-Zeliger
authors.affiliation: Department of Immunology, Weizmann Institute of Science, Herzel St 1, Rehovot 76100, Israel.
authors.forename: Nir
authors.initials: N
authors.lastname: Friedman
authors.affiliation: Department of Immunology, Weizmann Institute of Science, Herzel St 1, Rehovot 76100, Israel.
authors.forename: Rina
authors.initials: R
authors.lastname: Aharoni
authors.affiliation: Department of Immunology, Weizmann Institute of Science, Herzel St 1, Rehovot 76100, Israel.
authors.forename: Ruth
authors.initials: R
authors.lastname: Arnon
authors.affiliation: Department of Immunology, Weizmann Institute of Science, Herzel St 1, Rehovot 76100, Israel.
authors.forename: Oren
authors.initials: O
authors.lastname: Yifa
authors.affiliation: Department of Immunology, Weizmann Institute of Science, Herzel St 1, Rehovot 76100, Israel.
authors.forename: Anna
authors.initials: A
authors.lastname: Aronovich
authors.affiliation: Department of Immunology, Weizmann Institute of Science, Herzel St 1, Rehovot 76100, Israel. Electronic address: yair.reisner@weizmann.ac.il.
authors.forename: Yair
authors.initials: Y
authors.lastname: Reisner
mesh_terms: D000273:Adipose Tissue / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D019264:Adoptive Transfer; D000818:Animals; D000943:Antigens, Differentiation / Q000032:analysis; D015551:Autoimmunity / Q000276:immunology*; D039521:CD11c Antigen / Q000032:analysis; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology / Q000637:transplantation; D002999:Clone Cells / Q000276:immunology; D003594:Cytoplasmic Granules / Q000737:chemistry; D003713:Dendritic Cells / Q000145:classification / Q000276:immunology* / Q000648:ultrastructure; D059305:Diet, High-Fat / Q000009:adverse effects; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology / Q000473:pathology; D005260:Female; D007249:Inflammation / Q000276:immunology* / Q000473:pathology; D008212:Lymphocyte Depletion; D008297:Male; D024821:Metabolic Syndrome / Q000209:etiology / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009765:Obesity / Q000276:immunology / Q000473:pathology; D010641:Phenotype; D052899:Pore Forming Cytotoxic Proteins / Q000032:analysis* / Q000172:deficiency / Q000235:genetics; D011828:Radiation Chimera; D017634:Self Tolerance / Q000276:immunology
chemical_list: D000943:Antigens, Differentiation; D039521:CD11c Antigen; D052899:Pore Forming Cytotoxic Proteins; C483886:perforin, mouse