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Publication : A bacterial bile acid metabolite modulates T<sub>reg</sub> activity through the nuclear hormone receptor NR4A1.

First Author  Li W Year  2021
Journal  Cell Host Microbe Volume  29
Issue  9 Pages  1366-1377.e9
PubMed ID  34416161 Mgi Jnum  J:320606
Mgi Id  MGI:6874709 Doi  10.1016/j.chom.2021.07.013
Citation  Li W, et al. (2021) A bacterial bile acid metabolite modulates Treg activity through the nuclear hormone receptor NR4A1. Cell Host Microbe 29(9):1366-1377.e9
abstractText  Bile acids act as signaling molecules that regulate immune homeostasis, including the differentiation of CD4(+) T cells into distinct T cell subsets. The bile acid metabolite isoallolithocholic acid (isoalloLCA) enhances the differentiation of anti-inflammatory regulatory T cells (Treg cells) by facilitating the formation of a permissive chromatin structure in the promoter region of the transcription factor forkhead box P3 (Foxp3). Here, we identify gut bacteria that synthesize isoalloLCA from 3-oxolithocholic acid and uncover a gene cluster responsible for the conversion in members of the abundant human gut bacterial phylum Bacteroidetes. We also show that the nuclear hormone receptor NR4A1 is required for the effect of isoalloLCA on Treg cells. Moreover, the levels of isoalloLCA and its biosynthetic genes are significantly reduced in patients with inflammatory bowel diseases, suggesting that isoalloLCA and its bacterial producers may play a critical role in maintaining immune homeostasis in humans.
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