: There is growing recognition that regionalization of bacterial colonization and immunity along the intestinal tract has an important role in health and disease. Yet, the mechanisms underlying intestinal regionalization and its dysregulation in disease are not well understood. This study found that regional epithelial expression of the transcription factor GATA4 controls bacterial colonization and inflammatory tissue immunity in the proximal small intestine by regulating retinol metabolism and luminal IgA. Furthermore, in mice without jejunal GATA4 expression, the commensal segmented filamentous bacteria promoted pathogenic inflammatory immune responses that disrupted barrier function and increased mortality upon Citrobacter rodentium infection. In celiac disease patients, low GATA4 expression was associated with metabolic alterations, mucosal Actinobacillus, and increased IL-17 immunity. Taken together, these results reveal broad impacts of GATA4-regulated intestinal regionalization on bacterial colonization and tissue immunity, highlighting an elaborate interdependence of intestinal metabolism, immunity, and microbiota in homeostasis and disease.
GATA4 controls regionalization of tissue immunity and commensal-driven immunopathology / Earley, Zachary M; Lisicka, Wioletta; Sifakis, Joseph J; Aguirre-Gamboa, Raúl; Kowalczyk, Anita; Barlow, Jacob T; Shaw, Dustin G; Discepolo, Valentina; Tan, Ineke L; Gona, Saideep; Ernest, Jordan D; Matzinger, Polly; Barreiro, Luis B; Morgun, Andrey; Bendelac, Albert; Ismagilov, Rustem F; Shulzhenko, Natalia; Riesenfeld, Samantha J; Jabri, Bana. - In: IMMUNITY. - ISSN 1097-4180. - 56:1(2023), pp. 43-57.e10. [10.1016/j.immuni.2022.12.009]
GATA4 controls regionalization of tissue immunity and commensal-driven immunopathology
Discepolo, Valentina;
2023
Abstract
: There is growing recognition that regionalization of bacterial colonization and immunity along the intestinal tract has an important role in health and disease. Yet, the mechanisms underlying intestinal regionalization and its dysregulation in disease are not well understood. This study found that regional epithelial expression of the transcription factor GATA4 controls bacterial colonization and inflammatory tissue immunity in the proximal small intestine by regulating retinol metabolism and luminal IgA. Furthermore, in mice without jejunal GATA4 expression, the commensal segmented filamentous bacteria promoted pathogenic inflammatory immune responses that disrupted barrier function and increased mortality upon Citrobacter rodentium infection. In celiac disease patients, low GATA4 expression was associated with metabolic alterations, mucosal Actinobacillus, and increased IL-17 immunity. Taken together, these results reveal broad impacts of GATA4-regulated intestinal regionalization on bacterial colonization and tissue immunity, highlighting an elaborate interdependence of intestinal metabolism, immunity, and microbiota in homeostasis and disease.File | Dimensione | Formato | |
---|---|---|---|
Early et al_GATAT4_Immunity_2023.pdf
solo utenti autorizzati
Tipologia:
Versione Editoriale (PDF)
Licenza:
Copyright dell'editore
Dimensione
4.71 MB
Formato
Adobe PDF
|
4.71 MB | Adobe PDF | Visualizza/Apri Richiedi una copia |
I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.