Neuropeptide regulation of non-redundant ILC2 responses at barrier surfaces

Amy M. Tsou, Hiroshi Yano, Christopher N. Parkhurst, Tanel Mahlakõiv, Coco Chu, Wen Zhang, Zhengxiang He, Katja J. Jarick, Connie Zhong, Gregory G. Putzel, Mai Hatazaki, Ivo C. Lorenz, David Andrew, Paul Balderes, Christoph S. N. Klose, Sergio A. Lira and David Artis ()
Additional contact information
Amy M. Tsou: Weill Cornell Medicine
Hiroshi Yano: Weill Cornell Medicine
Christopher N. Parkhurst: Weill Cornell Medicine
Tanel Mahlakõiv: Weill Cornell Medicine
Coco Chu: Weill Cornell Medicine
Wen Zhang: Weill Cornell Medicine
Zhengxiang He: Icahn School of Medicine at Mount Sinai
Katja J. Jarick: Infectious Diseases and Immunology
Connie Zhong: Weill Cornell Medicine
Gregory G. Putzel: Weill Cornell Medicine
Mai Hatazaki: Weill Cornell Medicine
Ivo C. Lorenz: Tri-Institutional Therapeutics Discovery Institute
David Andrew: Tri-Institutional Therapeutics Discovery Institute
Paul Balderes: Tri-Institutional Therapeutics Discovery Institute
Christoph S. N. Klose: Infectious Diseases and Immunology
Sergio A. Lira: Icahn School of Medicine at Mount Sinai
David Artis: Weill Cornell Medicine

Nature, 2022, vol. 611, issue 7937, 787-793

Abstract: Abstract Emerging studies indicate that cooperation between neurons and immune cells regulates antimicrobial immunity, inflammation and tissue homeostasis. For example, a neuronal rheostat provides excitatory or inhibitory signals that control the functions of tissue-resident group 2 innate lymphoid cells (ILC2s) at mucosal barrier surfaces1–4. ILC2s express NMUR1, a receptor for neuromedin U (NMU), which is a prominent cholinergic neuropeptide that promotes ILC2 responses5–7. However, many functions of ILC2s are shared with adaptive lymphocytes, including the production of type 2 cytokines8,9 and the release of tissue-protective amphiregulin (AREG)10–12. Consequently, there is controversy regarding whether innate lymphoid cells and adaptive lymphocytes perform redundant or non-redundant functions13–15. Here we generate a new genetic tool to target ILC2s for depletion or gene deletion in the presence of an intact adaptive immune system. Transgenic expression of iCre recombinase under the control of the mouse Nmur1 promoter enabled ILC2-specific deletion of AREG. This revealed that ILC2-derived AREG promotes non-redundant functions in the context of antiparasite immunity and tissue protection following intestinal damage and inflammation. Notably, NMU expression levels increased in inflamed intestinal tissues from both mice and humans, and NMU induced AREG production in mouse and human ILC2s. These results indicate that neuropeptide-mediated regulation of non-redundant functions of ILC2s is an evolutionarily conserved mechanism that integrates immunity and tissue protection.

Date: 2022
References: Add references at CitEc
Citations: View citations in EconPapers (2)

Downloads: (external link)
https://www.nature.com/articles/s41586-022-05297-6 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:611:y:2022:i:7937:d:10.1038_s41586-022-05297-6

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

DOI: 10.1038/s41586-022-05297-6

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 ().