Ron Put Posted April 14, 2021 Report Share Posted April 14, 2021 Not exactly new discovery, but a possible explanation of how it works:Fasting-induced FOXO4 blunts human CD4+ T helper cell responsivenessIntermittent fasting blunts inflammation in asthma1 and rheumatoid arthritis2, suggesting that fasting may be exploited as an immune-modulatory intervention. However, the mechanisms underpinning the anti-inflammatory effects of fasting are poorly characterized3–5. Here, we show that fasting in humans is sufficient to blunt CD4+ T helper cell responsiveness. RNA sequencing and flow cytometry immunophenotyping of peripheral blood mononuclear cells from volunteers subjected to overnight or 24-h fasting and 3 h of refeeding suggest that fasting blunts CD4+ T helper cell activation and differentiation. Transcriptomic analysis reveals that longer fasting has a more robust effect on CD4+ T-cell biology. Through bioinformatics analyses, we identify the transcription factor FOXO4 and its canonical target FK506-binding protein 5 (FKBP5) as a potential fasting-responsive regulatory axis. Genetic gain- or loss-of-function of FOXO4 and FKBP5 is sufficient to modulate TH1 and TH17 cytokine production. Moreover, we find that fasting-induced or genetic overexpression of FOXO4 and FKBP5 is sufficient to downregulate mammalian target of rapamycin complex 1 signalling and suppress signal transducer and activator of transcription 1/3 activation. Our results identify FOXO4–FKBP5 as a new fasting-induced, signal transducer and activator of transcription–mediated regulatory pathway to blunt human CD4+ T helper cell responsiveness. In a screen of peripheral blood cells from fasted or fed individuals, Han et al. identify FOXO4 and its target FKBP5 as fasting-induced modulators of CD4+ T helper cell responsiveness. Quote Link to comment Share on other sites More sharing options...
Clinton Posted April 15, 2021 Report Share Posted April 15, 2021 When it comes to inflammation ... Strike First Strike Hard No Mercy Quote Link to comment Share on other sites More sharing options...
Ron Put Posted April 15, 2021 Author Report Share Posted April 15, 2021 4 hours ago, Clinton said: No Mercy Yeah, inflammation has its role, but chronic inflammation is a killer, in most cases. But because obese people have massive chronic inflammation in general, they can survive some infections that might kill us skinny folks :) Quote Link to comment Share on other sites More sharing options...
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