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Brennan, Patrick

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Brennan

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Brennan, Patrick

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2013 - 20152

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Author's Publications: search.filters.isAuthorOfPublication.c3e51368-8533-4d94-96f2-cdd9b9a3640f

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    Shared and distinct transcriptional programs underlie the hybrid nature of iNKT cells
    (2013) Cohen, Nadia R.; Brennan, Patrick; Shay, Tal; Watts, Gerald; Brigl, Manfred; Kang, Joonsoo; Brenner, Michael
    Invariant natural killer T (iNKT) cells are innate-like T lymphocytes that act as critical regulators of the immune response. To better characterize this population, we profiled iNKT cell gene expression during ontogeny and in peripheral subsets as part of the Immunological Genome Project (ImmGen). High-resolution comparative transcriptional analyses defined developmental and subset-specific iNKT cell gene expression programs. In addition, iNKT cells were found to share an extensive transcriptional program with natural killer (NK) cells, similar in magnitude to that shared with major histocompatibility complex (MHC)-restricted T cells. Strikingly, the NK- iNKT program also operated constitutively in γδT cells and in adaptive T cells following activation. Together, our findings highlight a core effector program regulated distinctly in innate and adaptive lymphocytes.
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    Regulatory iNKT cells lack PLZF expression and control Treg cell and macrophage homeostasis in adipose tissue
    (2015) Lynch, Lydia; Michelet, Xavier; Zhang, Sai; Brennan, Patrick; Moseman, Ashley; Lester, Chantel; Besra, Gurdyal; Vomhof-Dekrey, Emilie E.; Tighe, Mike; Koay, Hui-Fern; Godfrey, Dale I.; Leadbetter, Elizabeth A.; Sant’Angelo, Derek B.; von Andrian-Werburg, Ulrich; Brenner, Michael
    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.