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The mechanism does not involve receptor downregulation or tolerance in any known way, but the signal-to-noise ratio is simply too low based on available evidence

Reducing intestinal barrier permeability attenuates arthritis Since our results suggested that increased zonulin levels along with impaired intestinal permeability for lactulose and FITC-Dextran (FD4) are preceding the onset of murine and human arthritis, we sought an intervention that strengthens the intestinal barrier and may disrupt the transition from autoimmunity to inflammation and thereby inhibit the onset of arthritis

10.1523/jneurosci.2478-06.2006 61 JovanovicJ

To recapitulate this model ex vivo, we treated slices with 1 mM CPZ and 15 ng/mL rapamycin continuously for 1 week, in an attempt to sustain CPZ-induced demyelination in the corpus callosum

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