IL-33 promotes an innate immune pathway of intestinal tissue protection dependent on amphiregulin-EGFR interactions

Monticelli, Laurel A.; Osborne, Lisa C.; Noti, Mario; Tran, Sara V.; Zaiss, Dietmar M. W.; Artis, David (2015). IL-33 promotes an innate immune pathway of intestinal tissue protection dependent on amphiregulin-EGFR interactions. Proceedings of the National Academy of Sciences of the United States of America - PNAS, 112(34), pp. 10762-10767. National Academy of Sciences NAS 10.1073/pnas.1509070112

[img] Text
PNAS-2015-Monticelli-10762-7.pdf - Published Version
Restricted to registered users only
Available under License Publisher holds Copyright.

Download (2MB)

The barrier surfaces of the skin, lung, and intestine are constantly exposed to environmental stimuli that can result in inflammation and tissue damage. Interleukin (IL)-33-dependent group 2 innate lymphoid cells (ILC2s) are enriched at barrier surfaces and have been implicated in promoting inflammation; however, the mechanisms underlying the tissue-protective roles of IL-33 or ILC2s at surfaces such as the intestine remain poorly defined. Here we demonstrate that, following activation with IL-33, expression of the growth factor amphiregulin (AREG) is a dominant functional signature of gut-associated ILC2s. In the context of a murine model of intestinal damage and inflammation, the frequency and number of AREG-expressing ILC2s increases following intestinal injury and genetic disruption of the endogenous AREG-epidermal growth factor receptor (EGFR) pathway exacerbated disease. Administration of exogenous AREG limited intestinal inflammation and decreased disease severity in both lymphocyte-sufficient and lymphocyte-deficient mice, revealing a previously unrecognized innate immune mechanism of intestinal tissue protection. Furthermore, treatment with IL-33 or transfer of ILC2s ameliorated intestinal disease severity in an AREG-dependent manner. Collectively, these data reveal a critical feedback loop in which cytokine cues from damaged epithelia activate innate immune cells to express growth factors essential for ILC-dependent restoration of epithelial barrier function and maintenance of tissue homeostasis.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Service Sector > Institute of Pathology > Immunopathology

UniBE Contributor:

Noti, Mario

ISSN:

0027-8424

Publisher:

National Academy of Sciences NAS

Language:

English

Submitter:

Doris Haefelin

Date Deposited:

07 Dec 2015 12:22

Last Modified:

05 Dec 2022 14:50

Publisher DOI:

10.1073/pnas.1509070112

PubMed ID:

26243875

Uncontrolled Keywords:

inflammatory bowel disease innate immunity innate lymphoid cell interleukin-33

BORIS DOI:

10.7892/boris.73738

URI:

https://boris.unibe.ch/id/eprint/73738

Actions (login required)

Edit item Edit item
Provide Feedback