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Nat Immunol. 2015 Jan;16(1):85-95. doi: 10.1038/ni.3047. Epub 2014 Dec 1.

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

Author information

1
Department of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Harvard Medical School, Boston, USA.
2
Department of Pediatrics, Rutgers Robert Wood Johnson Medical School, New Brunswick, New Jersey, USA.
3
Department of Microbiology and Immunology, Harvard Medical School, Boston, USA.
4
School of Biosciences, University of Birmingham, Edgbaston, Birmingham, UK.
5
Trudeau Institute, Saranac Lake, New York, USA.
6
1] Department of Microbiology &Immunology, Peter Doherty Institute, University of Melbourne, Parkville, Australia. [2] Australian Research Council Centre of Excellence for Advanced Molecular Imaging, University of Melbourne, Australia.
7
1] Department of Pediatrics, Rutgers Robert Wood Johnson Medical School, New Brunswick, New Jersey, USA. [2] Child Health Institute of New Jersey, Rutgers Robert Wood Johnson Medical School, New Brunswick, New Jersey, USA.

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.

PMID:
25436972
PMCID:
PMC4343194
DOI:
10.1038/ni.3047
[Indexed for MEDLINE]
Free PMC Article

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