Perforin-Positive Dendritic Cells Exhibit an Immuno-regulatory Role in Metabolic Syndrome and Autoimmunity

Yael Zlotnikov-Klionsky; Bar Nathansohn-Levi; Elias Shezen; Chava Rosen; Sivan Kagan; Liat Bar-On; Steffen Jung; Eric Shifrut; Shlomit Reich-Zeliger; Nir Friedman; Rina Aharoni; Ruth Arnon; Oren Yifa; Anna Aronovich; Yair Reisner

doi:10.1016/j.immuni.2015.08.015

Perforin-Positive Dendritic Cells Exhibit an Immuno-regulatory Role in Metabolic Syndrome and Autoimmunity

Immunity. 2015 Oct 20;43(4):776-87. doi: 10.1016/j.immuni.2015.08.015. Epub 2015 Sep 15.

Authors

Affiliations

¹ Department of Immunology, Weizmann Institute of Science, Herzel St 1, Rehovot 76100, Israel.
² Department of Immunology, Weizmann Institute of Science, Herzel St 1, Rehovot 76100, Israel. Electronic address: [email protected].

PMID: 26384546
DOI: 10.1016/j.immuni.2015.08.015

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adipose Tissue / immunology
Adipose Tissue / metabolism
Adipose Tissue / pathology
Adoptive Transfer
Animals
Antigens, Differentiation / analysis
Autoimmunity / immunology*
CD11c Antigen / analysis
CD8-Positive T-Lymphocytes / immunology*
CD8-Positive T-Lymphocytes / pathology
CD8-Positive T-Lymphocytes / transplantation
Clone Cells / immunology
Cytoplasmic Granules / chemistry
Dendritic Cells / classification
Dendritic Cells / immunology*
Dendritic Cells / ultrastructure
Diet, High-Fat / adverse effects
Encephalomyelitis, Autoimmune, Experimental / immunology
Encephalomyelitis, Autoimmune, Experimental / pathology
Female
Inflammation / immunology*
Inflammation / pathology
Lymphocyte Depletion
Male
Metabolic Syndrome / etiology
Metabolic Syndrome / immunology*
Metabolic Syndrome / pathology
Mice
Mice, Inbred C57BL
Mice, Transgenic
Obesity / immunology
Obesity / pathology
Phenotype
Pore Forming Cytotoxic Proteins / analysis*
Pore Forming Cytotoxic Proteins / deficiency
Pore Forming Cytotoxic Proteins / genetics
Radiation Chimera
Self Tolerance / immunology

Substances

Antigens, Differentiation
CD11c Antigen
Pore Forming Cytotoxic Proteins
perforin, mouse