Regulatory iNKT cells lack expression of the transcription factor PLZF and control the homeostasis of Treg cells and macrophages in adipose tissue

Lydia Lynch; Xavier Michelet; Sai Zhang; Patrick J Brennan; Ashley Moseman; Chantel Lester; Gurdyal Besra; Emilie E Vomhof-Dekrey; Mike Tighe; Hui-Fern Koay; Dale I Godfrey; Elizabeth A Leadbetter; Derek B Sant'Angelo; Ulrich von Andrian; Michael B Brenner

doi:10.1038/ni.3047

Regulatory iNKT cells lack expression of the transcription factor PLZF and control the homeostasis of Treg cells and macrophages in adipose tissue

Lydia Lynch, Xavier Michelet, Sai Zhang, Patrick J Brennan, Ashley Moseman, Chantel Lester, Gurdyal Besra, Emilie E Vomhof-Dekrey, Mike Tighe, Hui-Fern Koay, Dale I Godfrey, Elizabeth A Leadbetter, Derek B Sant'Angelo, Ulrich von Andrian, Michael B Brenner

Biosciences

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217 Citations (Scopus)

Abstract

Invariant natural killer T cells (iNKT cells) are lipid-sensing innate T cells that are restricted by the antigen-presenting molecule CD1d and express the transcription factor PLZF. iNKT cells accumulate in adipose tissue, where they are anti-inflammatory, but the factors that contribute to their anti-inflammatory nature, as well as their targets in adipose tissue, are unknown. Here we found that iNKT cells in adipose tissue had a unique transcriptional program and produced interleukin 2 (IL-2) and IL-10. Unlike other iNKT cells, they lacked PLZF but expressed the transcription factor E4BP4, which controlled their IL-10 production. The adipose iNKT cells were a tissue-resident population that induced an anti-inflammatory phenotype in macrophages and, through the production of IL-2, controlled the number, proliferation and suppressor function of regulatory T cells (Treg cells) in adipose tissue. Thus, iNKT cells in adipose tissue are unique regulators of immunological homeostasis in this tissue.

Original language	English
Journal	Nature Immunology
DOIs	https://doi.org/10.1038/ni.3047
Publication status	Published - 1 Dec 2014

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10.1038/ni.3047

Design, synthesis, and assessment of specific iNKT cell agonists for clinical applications
Besra, D., Cox, L., Cunningham, A. & Lammas, T.
Medical Research Council
1/03/12 → 29/02/16
Project: Research Councils

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Lynch, L., Michelet, X., Zhang, S., Brennan, P. J., Moseman, A., Lester, C., Besra, G., Vomhof-Dekrey, E. E., Tighe, M., Koay, H-F., Godfrey, D. I., Leadbetter, E. A., Sant'Angelo, D. B., von Andrian, U., & Brenner, M. B. (2014). Regulatory iNKT cells lack expression of the transcription factor PLZF and control the homeostasis of Treg cells and macrophages in adipose tissue. Nature Immunology. https://doi.org/10.1038/ni.3047

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title = "Regulatory iNKT cells lack expression of the transcription factor PLZF and control the homeostasis of Treg cells and macrophages in adipose tissue",

abstract = "Invariant natural killer T cells (iNKT cells) are lipid-sensing innate T cells that are restricted by the antigen-presenting molecule CD1d and express the transcription factor PLZF. iNKT cells accumulate in adipose tissue, where they are anti-inflammatory, but the factors that contribute to their anti-inflammatory nature, as well as their targets in adipose tissue, are unknown. Here we found that iNKT cells in adipose tissue had a unique transcriptional program and produced interleukin 2 (IL-2) and IL-10. Unlike other iNKT cells, they lacked PLZF but expressed the transcription factor E4BP4, which controlled their IL-10 production. The adipose iNKT cells were a tissue-resident population that induced an anti-inflammatory phenotype in macrophages and, through the production of IL-2, controlled the number, proliferation and suppressor function of regulatory T cells (Treg cells) in adipose tissue. Thus, iNKT cells in adipose tissue are unique regulators of immunological homeostasis in this tissue.",

author = "Lydia Lynch and Xavier Michelet and Sai Zhang and Brennan, {Patrick J} and Ashley Moseman and Chantel Lester and Gurdyal Besra and Vomhof-Dekrey, {Emilie E} and Mike Tighe and Hui-Fern Koay and Godfrey, {Dale I} and Leadbetter, {Elizabeth A} and Sant'Angelo, {Derek B} and {von Andrian}, Ulrich and Brenner, {Michael B}",

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day = "1",

doi = "10.1038/ni.3047",

language = "English",

journal = "Nature Immunology",

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Lynch, L, Michelet, X, Zhang, S, Brennan, PJ, Moseman, A, Lester, C, Besra, G, Vomhof-Dekrey, EE, Tighe, M, Koay, H-F, Godfrey, DI, Leadbetter, EA, Sant'Angelo, DB, von Andrian, U & Brenner, MB 2014, 'Regulatory iNKT cells lack expression of the transcription factor PLZF and control the homeostasis of Treg cells and macrophages in adipose tissue', Nature Immunology. https://doi.org/10.1038/ni.3047

TY - JOUR

T1 - Regulatory iNKT cells lack expression of the transcription factor PLZF and control the homeostasis of Treg cells and macrophages in adipose tissue

AU - Lynch, Lydia

AU - Michelet, Xavier

AU - Zhang, Sai

AU - Brennan, Patrick J

AU - Moseman, Ashley

AU - Lester, Chantel

AU - Besra, Gurdyal

AU - Vomhof-Dekrey, Emilie E

AU - Tighe, Mike

AU - Koay, Hui-Fern

AU - Godfrey, Dale I

AU - Leadbetter, Elizabeth A

AU - Sant'Angelo, Derek B

AU - von Andrian, Ulrich

AU - Brenner, Michael B

PY - 2014/12/1

Y1 - 2014/12/1

N2 - Invariant natural killer T cells (iNKT cells) are lipid-sensing innate T cells that are restricted by the antigen-presenting molecule CD1d and express the transcription factor PLZF. iNKT cells accumulate in adipose tissue, where they are anti-inflammatory, but the factors that contribute to their anti-inflammatory nature, as well as their targets in adipose tissue, are unknown. Here we found that iNKT cells in adipose tissue had a unique transcriptional program and produced interleukin 2 (IL-2) and IL-10. Unlike other iNKT cells, they lacked PLZF but expressed the transcription factor E4BP4, which controlled their IL-10 production. The adipose iNKT cells were a tissue-resident population that induced an anti-inflammatory phenotype in macrophages and, through the production of IL-2, controlled the number, proliferation and suppressor function of regulatory T cells (Treg cells) in adipose tissue. Thus, iNKT cells in adipose tissue are unique regulators of immunological homeostasis in this tissue.

AB - Invariant natural killer T cells (iNKT cells) are lipid-sensing innate T cells that are restricted by the antigen-presenting molecule CD1d and express the transcription factor PLZF. iNKT cells accumulate in adipose tissue, where they are anti-inflammatory, but the factors that contribute to their anti-inflammatory nature, as well as their targets in adipose tissue, are unknown. Here we found that iNKT cells in adipose tissue had a unique transcriptional program and produced interleukin 2 (IL-2) and IL-10. Unlike other iNKT cells, they lacked PLZF but expressed the transcription factor E4BP4, which controlled their IL-10 production. The adipose iNKT cells were a tissue-resident population that induced an anti-inflammatory phenotype in macrophages and, through the production of IL-2, controlled the number, proliferation and suppressor function of regulatory T cells (Treg cells) in adipose tissue. Thus, iNKT cells in adipose tissue are unique regulators of immunological homeostasis in this tissue.

U2 - 10.1038/ni.3047

DO - 10.1038/ni.3047

M3 - Article

C2 - 25436972

SN - 1529-2908

JO - Nature Immunology

JF - Nature Immunology

ER -

Regulatory iNKT cells lack expression of the transcription factor PLZF and control the homeostasis of Treg cells and macrophages in adipose tissue

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Design, synthesis, and assessment of specific iNKT cell agonists for clinical applications

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