Novel immunoregulatory role of perforin-positive dendritic cells

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...

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Bibliographic Details
Published in:Seminars in immunopathology 2017-02, Vol.39 (2), p.121-133
Main Authors: Orgad, Ran, Nathansohn-Levi, Bar, Kagan, Sivan, Zlotnikov Klionsky, Yael, Reisner, Yair
Format: Article
Language:English
Subjects:
Animals
Autoimmunity
Biomedical and Life Sciences
Biomedicine
Cell Differentiation
Cytotoxicity, Immunologic
Dendritic Cells - classification
Dendritic Cells - cytology
Dendritic Cells - immunology
Dendritic Cells - metabolism
Disease Models, Animal
Disease Susceptibility
Encephalomyelitis, Autoimmune, Experimental
Histocompatibility Antigens - immunology
Histocompatibility Antigens - metabolism
Humans
Immune Tolerance
Immunology
Immunomodulation
Internal Medicine
Metabolic Syndrome - etiology
Metabolic Syndrome - metabolism
Perforin - genetics
Perforin - metabolism
Review
Signal Transduction
T-Lymphocyte Subsets - immunology
T-Lymphocyte Subsets - metabolism
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Summary: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.
ISSN:1863-2297
1863-2300
DOI:10.1007/s00281-016-0589-6