ZBTB46 defines and regulates ILC3s that protect the intestine

Wenqing Zhou, Lei Zhou, Jordan Zhou, Coco Chu, Chao Zhang, Robbyn E. Sockolow, Gerard Eberl and Gregory F. Sonnenberg ()
Additional contact information
Wenqing Zhou: Cornell University
Lei Zhou: Cornell University
Jordan Zhou: Cornell University
Coco Chu: Cornell University
Chao Zhang: Boston University
Robbyn E. Sockolow: Cornell University
Gerard Eberl: Institut Pasteur
Gregory F. Sonnenberg: Cornell University

Nature, 2022, vol. 609, issue 7925, 159-165

Abstract: Abstract RORγt is a lineage-specifying transcription factor that is expressed by immune cells that are enriched in the gastrointestinal tract and promote immunity, inflammation and tissue homeostasis1–15. However, fundamental questions remain with regard to the cellular heterogeneity among these cell types, the mechanisms that control protective versus inflammatory properties and their functional redundancy. Here we define all RORγt+ immune cells in the intestine at single-cell resolution and identify a subset of group 3 innate lymphoid cells (ILC3s) that expresses ZBTB46, a transcription factor specifying conventional dendritic cells16–20. ZBTB46 is robustly expressed by CCR6+ lymphoid-tissue-inducer-like ILC3s that are developmentally and phenotypically distinct from conventional dendritic cells, and its expression is imprinted by RORγt, fine-tuned by microbiota-derived signals and increased by pro-inflammatory cytokines. ZBTB46 restrains the inflammatory properties of ILC3s, including the OX40L-dependent expansion of T helper 17 cells and the exacerbated intestinal inflammation that occurs after enteric infection. Finally, ZBTB46+ ILC3s are a major source of IL-22, and selective depletion of this population renders mice susceptible to enteric infection and associated intestinal inflammation. These results show that ZBTB46 is a transcription factor that is shared between conventional dendritic cells and ILC3s, and identify a cell-intrinsic function for ZBTB46 in restraining the pro-inflammatory properties of ILC3s and a non-redundant role for ZBTB46+ ILC3s in orchestrating intestinal health.

Date: 2022
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41586-022-04934-4 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:609:y:2022:i:7925:d:10.1038_s41586-022-04934-4

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

DOI: 10.1038/s41586-022-04934-4

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 ().