Immune microniches shape intestinal Treg function

Yisu Gu, Raquel Bartolomé-Casado, Chuan Xu, Alice Bertocchi, Alina Janney, Cornelia Heuberger, Claire F. Pearson, Sarah A. Teichmann, Emily E. Thornton () and Fiona Powrie ()
Additional contact information
Yisu Gu: University of Oxford
Raquel Bartolomé-Casado: Hinxton
Chuan Xu: Hinxton
Alice Bertocchi: University of Oxford
Alina Janney: University of Oxford
Cornelia Heuberger: University of Oxford
Claire F. Pearson: University of Oxford
Sarah A. Teichmann: Hinxton
Emily E. Thornton: University of Oxford
Fiona Powrie: University of Oxford

Nature, 2024, vol. 628, issue 8009, 854-862

Abstract: Abstract The intestinal immune system is highly adapted to maintaining tolerance to the commensal microbiota and self-antigens while defending against invading pathogens1,2. Recognizing how the diverse network of local cells establish homeostasis and maintains it in the complex immune environment of the gut is critical to understanding how tolerance can be re-established following dysfunction, such as in inflammatory disorders. Although cell and molecular interactions that control T regulatory (Treg) cell development and function have been identified3,4, less is known about the cellular neighbourhoods and spatial compartmentalization that shapes microorganism-reactive Treg cell function. Here we used in vivo live imaging, photo-activation-guided single-cell RNA sequencing5–7 and spatial transcriptomics to follow the natural history of T cells that are reactive towards Helicobacter hepaticus through space and time in the settings of tolerance and inflammation. Although antigen stimulation can occur anywhere in the tissue, the lamina propria—but not embedded lymphoid aggregates—is the key microniche that supports effector Treg (eTreg) cell function. eTreg cells are stable once their niche is established; however, unleashing inflammation breaks down compartmentalization, leading to dominance of CD103+SIRPα+ dendritic cells in the lamina propria. We identify and validate the putative tolerogenic interaction between CD206+ macrophages and eTreg cells in the lamina propria and identify receptor–ligand pairs that are likely to govern the interaction. Our results reveal a spatial mechanism of tolerance in the lamina propria and demonstrate how knowledge of local interactions may contribute to the next generation of tolerance-inducing therapies.

Date: 2024
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41586-024-07251-0 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:628:y:2024:i:8009:d:10.1038_s41586-024-07251-0

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/s41586-024-07251-0

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().