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Microbial Cgr2 will let your Th17 cells ROR(γT)

Naomi Rodriguez-Marino1, Luisa Cervantes-Barragan1

  • 1Department of Microbiology and Immunology, Emory University, Atlanta, GA, USA.

Cell Host & Microbe
|January 13, 2022
PubMed

Insights

Eggerthella lenta produces an enzyme that metabolizes RORγT inhibitors, increasing inflammation in colitis. Dietary arginine can neutralize this enzyme

Area of Science:

  • Microbiome-host interactions
  • Immunology
  • Gastroenterology

Background:

  • RORγT inhibitors are used to treat inflammatory conditions.
  • The gut bacterium Eggerthella lenta produces an enzyme called cardiac glycoside reductase 2 (cgr2).
  • The role of cgr2 in host immune responses and inflammatory diseases is not well understood.

Purpose of the Study:

  • To investigate the function of cgr2 in the context of colitis.
  • To determine how cgr2 influences the host immune system and inflammatory responses.

Main Methods:

  • In vitro enzymatic assays to study cgr2 activity.
  • Murine models of colitis to assess the in vivo effects of cgr2.
  • Analysis of immune cell populations, particularly Th17 cells.

Main Results:

  • cgr2 metabolizes RORγT inhibitors, reducing their efficacy.
  • Increased Th17 cell responses and heightened inflammation were observed in the presence of cgr2.
  • Dietary supplementation with arginine effectively neutralized the effect of cgr2, mitigating inflammation.

Conclusions:

  • The bacterial enzyme cgr2 plays a significant role in modulating host immune responses during colitis.
  • cgr2-mediated metabolism of RORγT inhibitors can exacerbate inflammation.
  • Arginine-rich diets represent a potential dietary intervention to counteract the pro-inflammatory effects of cgr2.

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