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

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^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

50 Scopus citations

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.

Original language	American English
Article number	3173
Pages (from-to)	776-787
Number of pages	12
Journal	Immunity
Volume	43
Issue number	4
DOIs	https://doi.org/10.1016/j.immuni.2015.08.015
State	Published - 20 Oct 2015
Externally published	Yes

Bibliographical note

Funding Information:
The authors wish to thank Dr. Eran Elinav for reviewing the manuscript and Dr. Hagit Shapiro, Dr. Yael Kuperman, and Dr. Michael Tsoory for professional advice. Y.R. holds the Henry Drake Professorial Chair in Transplantation Immunology. This work was supported in part by grants from BIRAX (Britain-Israel Research and Academic Exchange) Regenerative Medicine Initiative and ISF (no. 1346/14) and from Roberto and Renata Ruhman.

Publisher Copyright:
© 2015 Elsevier Inc.

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Zlotnikov-Klionsky, Y., Nathansohn-Levi, B., Shezen, E., Rosen, C., Kagan, S., Bar-On, L., Jung, S., Shifrut, E., Reich-Zeliger, S., Friedman, N., Aharoni, R., Arnon, R., Yifa, O., Aronovich, A., & Reisner, Y. (2015). Perforin-Positive Dendritic Cells Exhibit an Immuno-regulatory Role in Metabolic Syndrome and Autoimmunity. Immunity, 43(4), 776-787. Article 3173. https://doi.org/10.1016/j.immuni.2015.08.015

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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.",

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Zlotnikov-Klionsky, Y, Nathansohn-Levi, B, Shezen, E, Rosen, C, Kagan, S, Bar-On, L, Jung, S, Shifrut, E, Reich-Zeliger, S, Friedman, N, Aharoni, R, Arnon, R, Yifa, O, Aronovich, A & Reisner, Y 2015, 'Perforin-Positive Dendritic Cells Exhibit an Immuno-regulatory Role in Metabolic Syndrome and Autoimmunity', Immunity, vol. 43, no. 4, 3173, pp. 776-787. https://doi.org/10.1016/j.immuni.2015.08.015

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AU - Rosen, Chava

AU - Kagan, Sivan

AU - Bar-On, Liat

AU - Jung, Steffen

AU - Shifrut, Eric

AU - Reich-Zeliger, Shlomit

AU - Friedman, Nir

AU - Aharoni, Rina

AU - Arnon, Ruth

AU - Yifa, Oren

AU - Aronovich, Anna

AU - Reisner, Yair

N1 - Funding Information: The authors wish to thank Dr. Eran Elinav for reviewing the manuscript and Dr. Hagit Shapiro, Dr. Yael Kuperman, and Dr. Michael Tsoory for professional advice. Y.R. holds the Henry Drake Professorial Chair in Transplantation Immunology. This work was supported in part by grants from BIRAX (Britain-Israel Research and Academic Exchange) Regenerative Medicine Initiative and ISF (no. 1346/14) and from Roberto and Renata Ruhman. Publisher Copyright: © 2015 Elsevier Inc.

PY - 2015/10/20

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N2 - 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.

AB - 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.

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

Abstract

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