| Title: | Characterization of the pathoimmunology of necrotizing enterocolitis reveals novel therapeutic opportunities |
| Authors: | Cho, Steven X. Browse this author |
| Rudloff, Ina Browse this author |
| Lao, Jason C. Browse this author |
| Pang, Merrin A. Browse this author |
| Goldberg, Rimma Browse this author |
| Bui, Christine B. Browse this author |
| McLean, Catriona A. Browse this author |
| Stock, Magdalena Browse this author |
| Klassert, Tilman E. Browse this author |
| Slevogt, Hortense Browse this author |
| Mangan, Niamh E. Browse this author |
| Cheng, Wei Browse this author |
| Fischer, Doris Browse this author |
| Gfroerer, Stefan Browse this author |
| Sandhu, Manjeet K. Browse this author |
| Ngo, Devi Browse this author |
| Bujotzek, Alexander Browse this author |
| Lariviere, Laurent Browse this author |
| Schumacher, Felix Browse this author |
| Tiefenthaler, Georg Browse this author |
| Beker, Friederike Browse this author |
| Collins, Clare Browse this author |
| Kamlin, C. Omar F. Browse this author |
| Konig, Kai Browse this author |
| Malhotra, Atul Browse this author |
| Tan, Kenneth Browse this author |
| Theda, Christiane Browse this author |
| Veldman, Alex Browse this author |
| Ellisdon, Andrew M. Browse this author |
| Whisstock, James C. Browse this author |
| Berger, Philip J. Browse this author |
| Nold-Petry, Claudia A. Browse this author |
| Nold, Marcel F. Browse this author |
| Issue Date: | 13-Nov-2020 |
| Publisher: | Nature Research |
| Journal Title: | Nature communications |
| Volume: | 11 |
| Issue: | 1 |
| Start Page: | 5794 |
| Publisher DOI: | 10.1038/s41467-020-19400-w |
| Abstract: | 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. |
| Rights: | http://creativecommons.org/licenses/by/4.0/ |
| Type: | article |
| URI: | http://hdl.handle.net/2115/80435 |
| Appears in Collections: | 医学院・医学研究院 (Graduate School of Medicine / Faculty of Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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