ILC3s select microbiota-specific regulatory T cells to establish tolerance in the gut

Mengze Lyu, Hiroaki Suzuki, Lan Kang, Fabrina Gaspal, Wenqing Zhou, Jeremy Goc, Lei Zhou, Jordan Zhou, Wen Zhang, Zeli Shen, James G. Fox, Robbyn E. Sockolow, Terri M. Laufer, Yong Fan, Gerard Eberl, David R. Withers and Gregory F. Sonnenberg ()
Additional contact information
Mengze Lyu: Cornell University
Hiroaki Suzuki: Cornell University
Lan Kang: Cornell University
Fabrina Gaspal: University of Birmingham
Wenqing Zhou: Cornell University
Jeremy Goc: Cornell University
Lei Zhou: Cornell University
Jordan Zhou: Cornell University
Wen Zhang: Cornell University
Zeli Shen: Massachusetts Institute of Technology
James G. Fox: Massachusetts Institute of Technology
Robbyn E. Sockolow: Cornell University
Terri M. Laufer: University of Pennsylvania
Yong Fan: Allegheny Health Network
Gerard Eberl: Institut Pasteur
David R. Withers: University of Birmingham
Gregory F. Sonnenberg: Cornell University

Nature, 2022, vol. 610, issue 7933, 744-751

Abstract: Abstract Microbial colonization of the mammalian intestine elicits inflammatory or tolerogenic T cell responses, but the mechanisms controlling these distinct outcomes remain poorly understood, and accumulating evidence indicates that aberrant immunity to intestinal microbiota is causally associated with infectious, inflammatory and malignant diseases1–8. Here we define a critical pathway controlling the fate of inflammatory versus tolerogenic T cells that respond to the microbiota and express the transcription factor RORγt. We profiled all RORγt+ immune cells at single-cell resolution from the intestine-draining lymph nodes of mice and reveal a dominant presence of T regulatory (Treg) cells and lymphoid tissue inducer-like group 3 innate lymphoid cells (ILC3s), which co-localize at interfollicular regions. These ILC3s are distinct from extrathymic AIRE-expressing cells, abundantly express major histocompatibility complex class II, and are necessary and sufficient to promote microbiota-specific RORγt+ Treg cells and prevent their expansion as inflammatory T helper 17 cells. This occurs through ILC3-mediated antigen presentation, αV integrin and competition for interleukin-2. Finally, single-cell analyses suggest that interactions between ILC3s and RORγt+ Treg cells are impaired in inflammatory bowel disease. Our results define a paradigm whereby ILC3s select for antigen-specific RORγt+ Treg cells, and against T helper 17 cells, to establish immune tolerance to the microbiota and intestinal health.

Date: 2022
References: Add references at CitEc
Citations: View citations in EconPapers (5)

Downloads: (external link)
https://www.nature.com/articles/s41586-022-05141-x 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:610:y:2022:i:7933:d:10.1038_s41586-022-05141-x

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

DOI: 10.1038/s41586-022-05141-x

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 ().