Interleukin-22 signaling attenuates necrotizing enterocolitis by promoting epithelial cell regeneration

Belgacem Mihi; Qingqing Gong; Lila S. Nolan; Sarah E. Gale; Martin Goree; Elise Hu; Wyatt E. Lanik; Jamie M. Rimer; Victoria Liu; Olivia B. Parks; Angela N. Lewis; Pranjal Agrawal; Marie L. Laury; Pawan Kumar; Elizabeth Huang; Shay S. Bidani; Cliff J. Luke; Jay K. Kolls; Misty Good

doi:10.1016/j.xcrm.2021.100320

Interleukin-22 signaling attenuates necrotizing enterocolitis by promoting epithelial cell regeneration

Belgacem Mihi, Qingqing Gong, Lila S. Nolan, Sarah E. Gale, Martin Goree, Elise Hu, Wyatt E. Lanik, Jamie M. Rimer, Victoria Liu, Olivia B. Parks, Angela N. Lewis, Pranjal Agrawal, Marie L. Laury, Pawan Kumar, Elizabeth Huang, Shay S. Bidani, Cliff J. Luke, Jay K. Kolls, Misty Good

Research output: Contribution to journal › Article › peer-review

39 Scopus citations

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.

Original language	English
Article number	100320
Journal	Cell Reports Medicine
Volume	2
Issue number	6
DOIs	https://doi.org/10.1016/j.xcrm.2021.100320
State	Published - Jun 15 2021

Keywords

epithelial cells
interleukin-22
intestinal immunity
microbiome
necrotizing enterocolitis
neonatal
regeneration

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10.1016/j.xcrm.2021.100320

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Mihi, B., Gong, Q., Nolan, L. S., Gale, S. E., Goree, M., Hu, E., Lanik, W. E., Rimer, J. M., Liu, V., Parks, O. B., Lewis, A. N., Agrawal, P., Laury, M. L., Kumar, P., Huang, E., Bidani, S. S., Luke, C. J., Kolls, J. K., & Good, M. (2021). Interleukin-22 signaling attenuates necrotizing enterocolitis by promoting epithelial cell regeneration. Cell Reports Medicine, 2(6), Article 100320. https://doi.org/10.1016/j.xcrm.2021.100320

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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 = "Publisher Copyright: {\textcopyright} 2021 The Author(s)",

year = "2021",

month = jun,

day = "15",

doi = "10.1016/j.xcrm.2021.100320",

language = "English",

volume = "2",

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Mihi, B, Gong, Q, Nolan, LS, Gale, SE, Goree, M, Hu, E, Lanik, WE, Rimer, JM, Liu, V, Parks, OB, Lewis, AN, Agrawal, P, Laury, ML, Kumar, P, Huang, E, Bidani, SS, Luke, CJ, Kolls, JK & Good, M 2021, 'Interleukin-22 signaling attenuates necrotizing enterocolitis by promoting epithelial cell regeneration', Cell Reports Medicine, vol. 2, no. 6, 100320. https://doi.org/10.1016/j.xcrm.2021.100320

TY - JOUR

T1 - Interleukin-22 signaling attenuates necrotizing enterocolitis by promoting epithelial cell regeneration

AU - Mihi, Belgacem

AU - Gong, Qingqing

AU - Nolan, Lila S.

AU - Gale, Sarah E.

AU - Goree, Martin

AU - Hu, Elise

AU - Lanik, Wyatt E.

AU - Rimer, Jamie M.

AU - Liu, Victoria

AU - Parks, Olivia B.

AU - Lewis, Angela N.

AU - Agrawal, Pranjal

AU - Laury, Marie L.

AU - Kumar, Pawan

AU - Huang, Elizabeth

AU - Bidani, Shay S.

AU - Luke, Cliff J.

AU - Kolls, Jay K.

AU - Good, Misty

PY - 2021/6/15

Y1 - 2021/6/15

N2 - 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.

AB - 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.

KW - epithelial cells

KW - interleukin-22

KW - intestinal immunity

KW - microbiome

KW - necrotizing enterocolitis

KW - neonatal

KW - regeneration

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U2 - 10.1016/j.xcrm.2021.100320

DO - 10.1016/j.xcrm.2021.100320

M3 - Article

C2 - 34195684

AN - SCOPUS:85108000853

SN - 2666-3791

VL - 2

JO - Cell Reports Medicine

JF - Cell Reports Medicine

IS - 6

M1 - 100320

ER -

Interleukin-22 signaling attenuates necrotizing enterocolitis by promoting epithelial cell regeneration

Abstract

Keywords

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