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Article Dans Une Revue Proceedings of the National Academy of Sciences of the United States of America Année : 2023

Cross talk between Paneth and tuft cells drives dysbiosis and inflammation in the gut mucosa

Julie Nguyen
Salima Soualhi
Victoria Meslier
Mathieu Almeida
  • Fonction : Auteur
Benoit Quinquis
Florence Thirion
  • Fonction : Auteur
Fabien Herbert
Ali Lamrani
Laure Garnier
Florence Bernex

Résumé

Gut microbiota imbalance (dysbiosis) is increasingly associated with pathological conditions, both within and outside the gastrointestinal tract. Intestinal Paneth cells are considered to be guardians of the gut microbiota, but the events linking Paneth cell dysfunction with dysbiosis remain unclear. We report a three-step mechanism for dysbiosis initiation. Initial alterations in Paneth cells, as frequently observed in obese and inflammatorybowel diseases patients, cause a mild remodeling of microbiota, with amplification of succinate-producing species. SucnR1-dependent activation of epithelial tuft cells triggers a type 2 immune response that, in turn, aggravates the Paneth cell defaults, promoting dysbiosis and chronic inflammation. We thus reveal a function of tuft cells in promoting dysbiosis following Paneth cell deficiency and an unappreciated essential role of Paneth cells in maintaining a balanced microbiota to prevent inappropriate activation of tuft cells and deleterious dysbiosis. This succinate-tuft cell inflammation circuit may also contribute to the chronic dysbiosis observed in patients.
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Dates et versions

hal-04129050 , version 1 (16-06-2023)

Identifiants

Citer

Nathalie Coutry, Julie Nguyen, Salima Soualhi, François Gerbe, Victoria Meslier, et al.. Cross talk between Paneth and tuft cells drives dysbiosis and inflammation in the gut mucosa. Proceedings of the National Academy of Sciences of the United States of America, 2023, 120 (25), pp.e2219431120. ⟨10.1073/pnas.2219431120⟩. ⟨hal-04129050⟩
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