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 journalArticlepeer-review

191 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 languageEnglish (US)
Pages (from-to)85-95
Number of pages11
JournalNature Immunology
Volume16
Issue number1
DOIs
StatePublished - Dec 18 2015

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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