Transcription factor Nr4a1 couples sympathetic and inflammatory cues in CNS-recruited macrophages to limit neuroinflammation

Iftach Shaked, Richard N. Hanna, Helena Shaked, Grzegorz Chodaczek, Heba N. Nowyhed, George Tweet, Robert Tacke, Alp Bugra Basat, Zbigniew Mikulski, Susan Togher, Jacqueline Miller, Amy Blatchley, Shahram Salek-Ardakani, Martin Darvas, Minna U. Kaikkonen, Graham D. Thomas, Sonia Lai-Wing-Sun, Ayman Rezk, Amit Bar-Or, Christopher K. GlassHozefa Bandukwala, Catherine C. Hedrick

Research output: Contribution to journalArticlepeer-review

82 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)1228-1234
Number of pages7
JournalNature Immunology
Issue number12
StatePublished - Dec 1 2015
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


Dive into the research topics of 'Transcription factor Nr4a1 couples sympathetic and inflammatory cues in CNS-recruited macrophages to limit neuroinflammation'. Together they form a unique fingerprint.

Cite this