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

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 Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms Correspondence: Michael B. Brenner, MD: [email protected] and Lydia Lynch, PhD: [email protected]. Author Contributions: L.L. designed and performed experiments, analyzed data and wrote the paper; X.M., S.Z., A.M., C.L. and H.F.K. performed experiments; E.E.V.D, M.T. and E.A.L. developed analytical tools; P.J.B. contributed to the microarray analysis and other analysis, G.B. synthesized aGalCer, U.vA. D.I.G. and D.B.S’A. contributed to the design of experiments and provided materials and tools, and M.B.B. designed experiments and wrote the paper. HHS Public Access Author manuscript Nat Immunol. Author manuscript; available in PMC 2015 July 01. Published in final edited form as: Nat Immunol. 2015 January ; 16(1): 85–95. doi:10.1038/ni.3047. A uhor M anscript