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

2014; Nature Portfolio; Volume: 16; Issue: 1 Linguagem: Inglês

10.1038/ni.3047

1529-2916

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

IL-33, ST2, and ILC Pathways

iNKT cells in adipose tissue are anti-inflammatory. Brenner and colleagues show that adipose iNKT cells have a unique transcriptional program, produce IL-2 and IL-10 and lack expression of the transcription factor PLZF. 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.