@article{b266a119e8654ff385bcfdb520ec281e,
title = "Interleukin-22 signaling attenuates necrotizing enterocolitis by promoting epithelial cell regeneration",
abstract = "Necrotizing enterocolitis (NEC) is a deadly intestinal inflammatory disorder that primarily affects premature infants and lacks adequate therapeutics. Interleukin (IL)-22 plays a critical role in gut barrier maintenance, promoting epithelial regeneration, and controlling intestinal inflammation in adult animal models. However, the importance of IL-22 signaling in neonates during NEC remains unknown. We investigated the role of IL-22 in the neonatal intestine under homeostatic and inflammatory conditions by using a mouse model of NEC. Our data reveal that Il22 expression in neonatal murine intestine is negligible until weaning, and both human and murine neonates lack IL-22 production during NEC. Mice deficient in IL-22 or lacking the IL-22 receptor in the intestine display a similar susceptibility to NEC, consistent with the lack of endogenous IL-22 during development. Strikingly, treatment with recombinant IL-22 during NEC substantially reduces inflammation and enhances epithelial regeneration. These findings may provide a new therapeutic strategy to attenuate NEC.",
keywords = "epithelial cells, interleukin-22, intestinal immunity, microbiome, necrotizing enterocolitis, neonatal, regeneration",
author = "Belgacem Mihi and Qingqing Gong and Nolan, {Lila S.} and Gale, {Sarah E.} and Martin Goree and Elise Hu and Lanik, {Wyatt E.} and Rimer, {Jamie M.} and Victoria Liu and Parks, {Olivia B.} and Lewis, {Angela N.} and Pranjal Agrawal and Laury, {Marie L.} and Pawan Kumar and Elizabeth Huang and Bidani, {Shay S.} and Luke, {Cliff J.} and Kolls, {Jay K.} and Misty Good",
note = "Funding Information: This manuscript was supported by R01DK118568 (M. Good), R03DK111473 (M. Good), K08DK101608 (M. Good), and 5T32HD043010 (L.S.N.) from the National Institutes of Health; March of Dimes Foundation grant 5-FY17-79 (M. Good); American Academy of Pediatrics Marshall Klaus Award (L.S.N.); the St. Louis Children's Hospital Foundation (M. Good); The Children's Discovery Institute of Washington University and St. Louis Children's Hospital (M. Good); and the Department of Pediatrics at Washington University School of Medicine, St. Louis. We would like to thank the Genome Technology Access Center in the Department of Genetics at Washington University School of Medicine for help with 16S analysis. The Center is partially supported by NCI Cancer Center Support grant P30 CA91842 to the Siteman Cancer Center and by the ICTS/CTSA grant UL1TR002345 from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH), and NIH Roadmap for Medical Research. We would also like to thank the Washington University Digestive Diseases Research Center Core for histology services supported by NIH grant P30 DK052574. Histological imaging was performed in part through the use of Washington University Center for Cellular Imaging (WUCCI) supported by The Children's Discovery Institute of Washington University and St. Louis Children's Hospital (CDI-CORE-2019-813). This publication is solely the responsibility of the authors and does not necessarily represent the official view of NCRR, NIH, or any of the funders. Conceptualization, B.M. J.K.K. and M. Good; methodology, all authors; investigation, all authors; writing ? original draft, B.M. and M. Good; writing ? review & editing, all authors; funding acquisition, L.S.N. and M. Good; resources, J.K.K. and M. Good; supervision, B.M. and M. Good. Drs. J.K.K. and M. Good have a patent pending on the use of IL-22 to prevent or treat NEC. Dr. M. Good has received sponsored research agreement funding from Astarte Medical, Evive Biotech, and Takeda Pharmaceuticals. Dr. M. Good also serves on the Scientific Advisory Council of the NEC Society and the Clinical and Technology Advisory Board of Astarte Medical. She also participated in a neonatal microbiome advisory board for Abbott Laboratories in 2019. None of these sources had any role in this study. Funding Information: This manuscript was supported by R01DK118568 (M. Good), R03DK111473 (M. Good), K08DK101608 (M. Good), and 5T32HD043010 (L.S.N.) from the National Institutes of Health ; March of Dimes Foundation grant 5-FY17-79 (M. Good); American Academy of Pediatrics Marshall Klaus Award (L.S.N.); the St. Louis Children{\textquoteright}s Hospital Foundation (M. Good); The Children{\textquoteright}s Discovery Institute of Washington University and St. Louis Children{\textquoteright}s Hospital (M. Good); and the Department of Pediatrics at Washington University School of Medicine, St. Louis . Funding Information: Drs. J.K.K. and M. Good have a patent pending on the use of IL-22 to prevent or treat NEC. Dr. M. Good has received sponsored research agreement funding from Astarte Medical, Evive Biotech, and Takeda Pharmaceuticals. Dr. M. Good also serves on the Scientific Advisory Council of the NEC Society and the Clinical and Technology Advisory Board of Astarte Medical. She also participated in a neonatal microbiome advisory board for Abbott Laboratories in 2019. None of these sources had any role in this study. Funding Information: We would like to thank the Genome Technology Access Center in the Department of Genetics at Washington University School of Medicine for help with 16S analysis. The Center is partially supported by NCI Cancer Center Support grant P30 CA91842 to the Siteman Cancer Center and by the ICTS/CTSA grant UL1TR002345 from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH), and NIH Roadmap for Medical Research . We would also like to thank the Washington University Digestive Diseases Research Center Core for histology services supported by NIH grant P30 DK052574 . Histological imaging was performed in part through the use of Washington University Center for Cellular Imaging (WUCCI) supported by The Children{\textquoteright}s Discovery Institute of Washington University and St. Louis Children{\textquoteright}s Hospital ( CDI-CORE-2019-813 ). This publication is solely the responsibility of the authors and does not necessarily represent the official view of NCRR, NIH, or any of the funders. Publisher Copyright: {\textcopyright} 2021 The Author(s)",
year = "2021",
month = jun,
day = "15",
doi = "10.1016/j.xcrm.2021.100320",
language = "English",
volume = "2",
journal = "Cell Reports Medicine",
issn = "2666-3791",
number = "6",
}