Characterization of the pathoimmunology of necrotizing enterocolitis reveals novel therapeutic opportunities

Cho, Steven X.; Rudloff, Ina; Lao, Jason C. et al.

Nature communications, 2020, 11(1), 5794

Permalink : https://hdl.handle.net/2115/80435

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https://doi.org/10.1038/s41467-020-19400-w     95

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アクセス権
open access
URI
https://hdl.handle.net/2115/80435
タイトル
Characterization of the pathoimmunology of necrotizing enterocolitis reveals novel therapeutic opportunities
著者
Cho, Steven X. ; Rudloff, Ina ; Lao, Jason C. ; Pang, Merrin A. ; Goldberg, Rimma ; Bui, Christine B. ; McLean, Catriona A. ; Stock, Magdalena ; Klassert, Tilman E. ; Slevogt, Hortense ; Mangan, Niamh E. ; Cheng, Wei ; Fischer, Doris ; Gfroerer, Stefan ; Sandhu, Manjeet K. ; Ngo, Devi ; Bujotzek, Alexander ; Lariviere, Laurent ; Schumacher, Felix ; Tiefenthaler, Georg ; Beker, Friederike ; Collins, Clare ; Kamlin, C. Omar F. ; Konig, Kai ; Malhotra, Atul ; Tan, Kenneth ; Theda, Christiane ; Veldman, Alex ; Ellisdon, Andrew M. ; Whisstock, James C. ; Berger, Philip J. ; Nold-Petry, Claudia A. ; Nold, Marcel F.
著者名
Cho, Steven X.
著者名
Rudloff, Ina
著者名
Lao, Jason C.
著者名
Pang, Merrin A.
著者名
Goldberg, Rimma
著者名
Bui, Christine B.
著者名
McLean, Catriona A.
著者名
Stock, Magdalena
著者名
Klassert, Tilman E.
著者名
Slevogt, Hortense
著者名
Mangan, Niamh E.
著者名
Cheng, Wei
著者名
Fischer, Doris
著者名
Gfroerer, Stefan
著者名
Sandhu, Manjeet K.
著者名
Ngo, Devi
著者名
Bujotzek, Alexander
著者名
Lariviere, Laurent
著者名
Schumacher, Felix
著者名
Tiefenthaler, Georg
著者名
Beker, Friederike
著者名
Collins, Clare
著者名
Kamlin, C. Omar F.
著者名
Konig, Kai
著者名
Malhotra, Atul
著者名
Tan, Kenneth
著者名
Theda, Christiane
著者名
Veldman, Alex
著者名
Ellisdon, Andrew M.
著者名
Whisstock, James C.
著者名
Berger, Philip J.
著者名
Nold-Petry, Claudia A.
著者名
Nold, Marcel F.
言語
英語
発行日
2020-11-13
出版者
Nature Research
収録物名
Nature communications
巻(号)
11(1)
ページ
5794
抄録
Necrotizing enterocolitis (NEC) is a severe, currently untreatable intestinal disease that predominantly affects preterm infants and is driven by poorly characterized inflammatory pathways. Here, human and murine NEC intestines exhibit an unexpected predominance of type 3/T(H)17 polarization. In murine NEC, pro-inflammatory type 3 NKp46(-)ROR gamma t(+)Tbet(+) innate lymphoid cells (ILC3) are 5-fold increased, whereas ILC1 and protective NKp46(+)ROR gamma t(+) ILC3 are obliterated. Both species exhibit dysregulation of intestinal TLR repertoires, with TLR4 and TLR8 increased, but TLR5-7 and TLR9-12 reduced. Transgenic IL-37 effectively protects mice from intestinal injury and mortality, whilst exogenous IL-37 is only modestly efficacious. Mechanistically, IL-37 favorably modulates immune homeostasis, TLR repertoires and microbial diversity. Moreover, IL-37 and its receptor IL-1R8 are reduced in human NEC epithelia, and IL-37 is lower in blood monocytes from infants with NEC and/or lower birthweight. Our results on NEC pathomechanisms thus implicate type 3 cytokines, TLRs and IL-37 as potential targets for novel NEC therapies.
資源タイプ
学術雑誌論文
出版タイプ
Version of Record
権利情報
Creative Commons Attribution 4.0 International
PISSN
2041-1723
関連情報 (isIdenticalTo)
出版社版DOI
https://doi.org/10.1038/s41467-020-19400-w