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Regulatory iNKT cells lack PLZF expression and control Treg cell and macrophage homeostasis in adipose tissue

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2015

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Lynch, L., X. Michelet, S. Zhang, P. J. Brennan, A. Moseman, C. Lester, G. Besra, et al. 2015. “Regulatory iNKT cells lack PLZF expression and control Treg cell and macrophage homeostasis in adipose tissue.” Nature immunology 16 (1): 85-95. doi:10.1038/ni.3047. http://dx.doi.org/10.1038/ni.3047.

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iNKT cells are CD1d-restricted lipid-sensing innate T cells that 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, and their targets in adipose tissue are unknown. Here we report that adipose tissue iNKT cells have a unique transcriptional program and produce interleukin 2 (IL-2) and IL-10. Unlike other iNKT cells, they lack PLZF, but express the transcription factor E4BP4, which controls their IL-10 production. Adipose iNKT cells are a tissue resident population that induces an anti-inflammatory phenotype in macrophages and, through production of IL-2, controls the number, proliferation and suppressor function of adipose regulatory T (Treg) cells. Thus, adipose tissue iNKT cells are unique regulators of immune homeostasis in this tissue.

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