A short but very interesting paper in Journal of Immunology caught my attention this week. In this study the scientists showed that butyrate, a short chain fatty acid derived from fiber fermentation by microbiota acts on GPR41 receptor in the thymus to increase Aire expression and amplify Foxp3+ Treg frequency (of note, compared to WT, GPR41-KO thymus already contains almost 5-fold less Tregs).
Generally it is believed that microbiota works locally in the gut or other peripheral tissues to either convert naive T cells into Foxp3+ Tregs or expand existing Treg numbers. However no one yet managed to definitely show which pathway is functionally operational in vivo in physiological conditions. This study now could help to further narrow down biological mechanisms responsible for Treg biology. If microbiota-generated butyrate could work on thymus to increase Aire expression that in turn increases level of Thymus-derived Treg generation, then peripheral conversion pathway may play even less relevant role in physiological mechanisms of tolerance.
The most obvious question after reading this article is why the authors did not test Aire KO mice to verify their conclusions.
posted by David Usharauli
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