| First Author | Alexander M | Year | 2022 |
| Journal | Cell Host Microbe | Volume | 30 |
| Issue | 1 | Pages | 17-30.e9 |
| PubMed ID | 34822777 | Mgi Jnum | J:336912 |
| Mgi Id | MGI:6874674 | Doi | 10.1016/j.chom.2021.11.001 |
| Citation | Alexander M, et al. (2022) Human gut bacterial metabolism drives Th17 activation and colitis. Cell Host Microbe 30(1):17-30.e9 |
| abstractText | Bacterial activation of T helper 17 (Th17) cells exacerbates mouse models of autoimmunity, but how human-associated bacteria impact Th17-driven disease remains elusive. We show that human gut Actinobacterium Eggerthella lenta induces intestinal Th17 activation by lifting inhibition of the Th17 transcription factor Rorgammat through cell- and antigen-independent mechanisms. E. lenta is enriched in inflammatory bowel disease (IBD) patients and worsens colitis in a Rorc-dependent manner in mice. Th17 activation varies across E. lenta strains, which is attributable to the cardiac glycoside reductase 2 (Cgr2) enzyme. Cgr2 is sufficient to induce interleukin (IL)-17a, a major Th17 cytokine. cgr2+ E. lenta deplete putative steroidal glycosides in pure culture; related compounds are negatively associated with human IBD severity. Finally, leveraging the sensitivity of Cgr2 to dietary arginine, we prevented E. lenta-induced intestinal inflammation in mice. Together, these results support a role for human gut bacterial metabolism in driving Th17-dependent autoimmunity. |
