Linking stress to immune function

Shaked I, Hanna RN, Shaked H, Chodaczek G, Nowyhed HN, Tweet G, Tacke R, Basat AB, Mikulski Z, Togher S, Miller J, Blatchley A, Salek-Ardakani S, Darvas M, Kaikkonen MU, Thomas GD, Lai-Wing-Sun S, Rezk A, Bar-Or A, Glass CK, Bandukwala H, Hedrick CC.
Nat Immunol. 2015 Nov 2. doi: 10.1038/ni.3321. [Epub ahead of print]
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)/adrenaline in macrophages and thereby limited experimental autoimmune encephalomyelitis (EAE), a mouse model of multiple sclerosis. Lack of Nr4a1 in macrophages led to enhanced NE production, accelerated infiltration of leucocytes into the central nervous system (CNS) and disease exacerbation in vivo. In contrast, macrophage-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.

Catecholamines are water-soluble and are 50%-bound to plasma proteins in circulation. Included among catecholamines are: epinephrine (adrenaline), norepinephrine (noradrenaline) and dopamine; all of which are produced from phenylalanine and tyrosine. In this study they find that regulation of a transcription factor in macrophages limited their ability to be involved in neuroinflammation and their production of adrenaline. This is the hormone involved in the fight or flight response. Is this the link with stress you have been asking about?

A corepressor does not directly bind to DNA, but instead indirectly regulates gene expression by binding to repressors.The repressor in turn binds to a gene promoter (a sequence of DNAadjacent to the regulated gene), thereby blocking transcription of that gene.
Control group = abit of a limp tail…so according to Jaz “The only way is up”

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  • While this is WAY beyond my knowledge set as a programmer (if? Else? Else If? Not? And? Or?) it is really AMAZING how all these complex systems work together! I do learn something new from BARTS all the time, thank you for this!

    I did not see a comment form on the "3 Day Miracle". Notice, we as a prepubescent MS web entity reported? Nothing on it. Reasoning: 1. I am a programmer, logic says this is an anomaly and while clearly something happened, clearly, a great deal more did not. 2. It appeared quite sensationalist… As Prof G. said, cant be counterproductive. I have my own phrase however, "Many things that make headlines cause other people to get lines in their forehead". Was rather surprised at some of the entities reporting on it. He does take LDN.

    Lastly, at an MS Event 48 hours ago we were seated at a table with some interesting folks. One gentlemen with PPMS in a powered chair. He sings wonderful gospel music. Diagnosed some 25 years back w/ PPMS he attributes eating well, exercise and his faith in purpose to be the reason over those 25 years his progression is less than most.

    Another, a women diagnosed back in 1991 I was astonished by. RRMS, 24 years and she takes Methotrexate prescribed by her Neuro. The Neuro we know well, an extremely well credentialed Neuro. Here in the US -> A most do the FDA laundry list of meds and only under unresponsive circumstance might they stray. She's been on Methotrexate for 24 years and said she's had only 3 flare's during all that time.

  • I know many MSers who claim to have outbreaks or worsening of symptoms after "emotionally stressful events" … I even agree that emotional stress is a 'trigger' for these activity peaks of the disease. Just wanted to understand if it would be plausible to cases of MS juvenile or child … I see more and more cases being diagnosed in adolescents between 13 and 18 years old …

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