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Rezende, Rafael M.; Cox, Laura M.; Moreira, Thais G.; Liu, Shirong; Boulenouar, Selma; Dhang, Fyonn; LeServe, Danielle S.; Nakagaki, Brenda N.; Lopes, Juliana R.; Tatematsu, Bruna K.; Lemos, Luisa; Mayrink, Julia; Lobo, Eduardo L. C.; Guo, Lydia; Oliveira, Marilia G.; Kuhn, Chantal; Weiner, Howard L.

Gamma-delta T cells modulate the microbiota and fecal micro-RNAs to maintain mucosal tolerance

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  • Media type: E-Article
  • Title: Gamma-delta T cells modulate the microbiota and fecal micro-RNAs to maintain mucosal tolerance
  • Contributor: Rezende, Rafael M.; Cox, Laura M.; Moreira, Thais G.; Liu, Shirong; Boulenouar, Selma; Dhang, Fyonn; LeServe, Danielle S.; Nakagaki, Brenda N.; Lopes, Juliana R.; Tatematsu, Bruna K.; Lemos, Luisa; Mayrink, Julia; Lobo, Eduardo L. C.; Guo, Lydia; Oliveira, Marilia G.; Kuhn, Chantal; Weiner, Howard L.
  • imprint: Springer Science and Business Media LLC, 2023
  • Published in: Microbiome
  • Language: English
  • DOI: 10.1186/s40168-023-01478-1
  • ISSN: 2049-2618
  • Origination:
  • Footnote:
  • Description: <jats:title>Abstract</jats:title><jats:sec> <jats:title>Background</jats:title> <jats:p>Gamma-delta (γδ) T cells are a major cell population in the intestinal mucosa and are key mediators of mucosal tolerance and microbiota composition. Little is known about the mechanisms by which intestinal γδ T cells interact with the gut microbiota to maintain tolerance.</jats:p> </jats:sec><jats:sec> <jats:title>Results</jats:title> <jats:p>We found that antibiotic treatment impaired oral tolerance and depleted intestinal γδ T cells, suggesting that the gut microbiota is necessary to maintain γδ T cells. We also found that mice deficient for γδ T cells (γδ<jats:sup>−/−</jats:sup>) had an altered microbiota composition that led to small intestine (SI) immune dysregulation and impaired tolerance. Accordingly, colonizing WT mice with γδ<jats:sup>−/−</jats:sup> microbiota resulted in SI immune dysregulation and loss of tolerance whereas colonizing γδ<jats:sup>−/−</jats:sup> mice with WT microbiota normalized mucosal immune responses and restored mucosal tolerance. Moreover, we found that SI γδ T cells shaped the gut microbiota and regulated intestinal homeostasis by secreting the fecal micro-RNA let-7f. Importantly, oral administration of let-7f to γδ<jats:sup>−/−</jats:sup> mice rescued mucosal tolerance by promoting the growth of the γδ<jats:sup>−/−</jats:sup>-microbiota-depleted microbe <jats:italic>Ruminococcus gnavus</jats:italic>.</jats:p> </jats:sec><jats:sec> <jats:title>Conclusions</jats:title> <jats:p>Taken together, we demonstrate that γδ T cell-selected microbiota is necessary and sufficient to promote mucosal tolerance, is mediated in part by γδ T cell secretion of fecal micro-RNAs, and is mechanistically linked to restoration of mucosal immune responses.</jats:p> </jats:sec>
  • Access State: Open Access