Regulatory iNKT cells lack expression of the transcription factor PLZF and control the homeostasis of T reg 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 T reg 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

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

320 Scopus citations

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 (T reg cells) in adipose tissue. Thus, iNKT cells in adipose tissue are unique regulators of immunological homeostasis in this tissue.

Original language	English (US)
Pages (from-to)	85-95
Number of pages	11
Journal	Nature Immunology
Volume	16
Issue number	1
DOIs	https://doi.org/10.1038/ni.3047
State	Published - Dec 18 2015
Externally published	Yes

All Science Journal Classification (ASJC) codes

Immunology and Allergy
Immunology

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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. (2015). Regulatory iNKT cells lack expression of the transcription factor PLZF and control the homeostasis of T reg cells and macrophages in adipose tissue. Nature Immunology, 16(1), 85-95. 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 T reg 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 (T reg 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 Koay, {Hui Fern} and Godfrey, {Dale I.} and Leadbetter, {Elizabeth A.} and Sant'Angelo, {Derek B.} and {Von Andrian}, Ulrich and Brenner, {Michael B.}",

note = "Publisher Copyright: {\textcopyright} 2015 Nature America, Inc.",

year = "2015",

month = dec,

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doi = "10.1038/ni.3047",

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Lynch, L, Michelet, X, Zhang, S, Brennan, PJ, Moseman, A, Lester, C, Besra, G, Vomhof-Dekrey, EE, Tighe, M, Koay, HF, Godfrey, DI, Leadbetter, EA, Sant'Angelo, DB, Von Andrian, U & Brenner, MB 2015, 'Regulatory iNKT cells lack expression of the transcription factor PLZF and control the homeostasis of T reg cells and macrophages in adipose tissue', Nature Immunology, vol. 16, no. 1, pp. 85-95. https://doi.org/10.1038/ni.3047

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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 - 2015/12/18

Y1 - 2015/12/18

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 (T reg cells) in adipose tissue. Thus, iNKT cells in adipose tissue are unique regulators of immunological homeostasis in this tissue.

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

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