IEC-intrinsic IL-1R signaling holds dual roles in regulating intestinal homeostasis and inflammation. J Exp Med 2023 Jun 05;220(6)
Date
03/29/2023Pubmed ID
36976181Pubmed Central ID
PMC10067527DOI
10.1084/jem.20212523Scopus ID
2-s2.0-85151168201 (requires institutional sign-in at Scopus site) 17 CitationsAbstract
Intestinal epithelial cells (IECs) constitute a critical first line of defense against microbes. While IECs are known to respond to various microbial signals, the precise upstream cues regulating diverse IEC responses are not clear. Here, we discover a dual role for IEC-intrinsic interleukin-1 receptor (IL-1R) signaling in regulating intestinal homeostasis and inflammation. Absence of IL-1R in epithelial cells abrogates a homeostatic antimicrobial program including production of antimicrobial peptides (AMPs). Mice deficient for IEC-intrinsic IL-1R are unable to clear Citrobacter rodentium (C. rodentium) but are protected from DSS-induced colitis. Mechanistically, IL-1R signaling enhances IL-22R-induced signal transducer and activator of transcription 3 (STAT3) phosphorylation in IECs leading to elevated production of AMPs. IL-1R signaling in IECs also directly induces expression of chemokines as well as genes involved in the production of reactive oxygen species. Our findings establish a protective role for IEC-intrinsic IL-1R signaling in combating infections but a detrimental role during colitis induced by epithelial damage.
Author List
Overcast GR, Meibers HE, Eshleman EM, Saha I, Waggoner L, Patel KN, Jain VG, Haslam DB, Alenghat T, VanDussen KL, Pasare CAuthor
Emily M. Eshleman PhD Assistant Professor in the Pediatrics department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsColitis
Epithelial Cells
Homeostasis
Inflammation
Intestinal Mucosa
Intestines
Mice
Receptors, Interleukin-1
