@article{6d1ec5a1b0214b5ea28493d32bcc6f78,
title = "Transcription factor Nr4a1 couples sympathetic and inflammatory cues in CNS-recruited macrophages to limit neuroinflammation",
abstract = "The molecular mechanisms that link the sympathetic stress response and inflammation remain obscure. Here we found that the transcription factor Nr4a1 regulated the production of norepinephrine (NE) in macrophages and thereby limited experimental autoimmune encephalomyelitis (EAE), a mouse model of multiple sclerosis. Lack of Nr4a1 in myeloid cells led to enhanced NE production, accelerated infiltration of leukocytes into the central nervous system (CNS) and disease exacerbation in vivo. In contrast, myeloid-specific deletion of tyrosine hydroxylase (TH), the rate-limiting enzyme in catecholamine biosynthesis, protected mice against EAE. Furthermore, we found that Nr4a1 repressed autocrine NE production in macrophages by recruiting the corepressor CoREST to the Th promoter. Our data reveal a new role for macrophages in neuroinflammation and identify Nr4a1 as a key regulator of catecholamine production by macrophages.",
author = "Iftach Shaked and Hanna, {Richard N.} and Helena Shaked and Grzegorz Chodaczek and Nowyhed, {Heba N.} and George Tweet and Robert Tacke and Basat, {Alp Bugra} and Zbigniew Mikulski and Susan Togher and Jacqueline Miller and Amy Blatchley and Shahram Salek-Ardakani and Martin Darvas and Kaikkonen, {Minna U.} and Thomas, {Graham D.} and Sonia Lai-Wing-Sun and Ayman Rezk and Amit Bar-Or and Glass, {Christopher K.} and Hozefa Bandukwala and Hedrick, {Catherine C.}",
note = "Funding Information: We thank D. Metzger (Institut G{\'e}n{\'e}tique Biologie Mol{\'e}culaire Cellulaire) and H. Ichinose (Tokyo Institute of Technology) for Nr4a1fl/fl mice; K. Ley for discussions; A. Rao for guidance in composing the manuscript; A. Crotti for guidance on microglia culture; and D. Yoakum for assistance with mouse colony management. Supported by the American Heart Association (13SDG17060117 to I.S. and 12SDG12070005 to R.N.H.), the La Jolla Institute Board of Directors (R.N.H.), Fondation Leducq (M.U.K.), the Sigrid Juselius Foundation (M.U.K.), the Academy of Finland (M.U.K.), the Pacific Northwest Udall Center (P50-NS062684 to M.D.) and the US National Institutes of Health (R01 DK091183-21 to C.K.G. and R01 HL118765 to C.C.H.). Publisher Copyright: {\textcopyright} 2015 Nature America, Inc.",
year = "2015",
month = dec,
day = "1",
doi = "10.1038/ni.3321",
language = "English (US)",
volume = "16",
pages = "1228--1234",
journal = "Nature Immunology",
issn = "1529-2908",
publisher = "Nature Publishing Group",
number = "12",
}