Paneth cell α-defensin misfolding correlates with dysbiosis and ileitis in Crohn's disease model mice.


Journal

Life science alliance
ISSN: 2575-1077
Titre abrégé: Life Sci Alliance
Pays: United States
ID NLM: 101728869

Informations de publication

Date de publication:
06 2020
Historique:
received: 29 10 2019
revised: 07 04 2020
accepted: 07 04 2020
entrez: 30 4 2020
pubmed: 30 4 2020
medline: 8 7 2021
Statut: epublish

Résumé

Crohn's disease (CD) is an intractable inflammatory bowel disease, and dysbiosis, disruption of the intestinal microbiota, is associated with CD pathophysiology. ER stress, disruption of ER homeostasis in Paneth cells of the small intestine, and α-defensin misfolding have been reported in CD patients. Because α-defensins regulate the composition of the intestinal microbiota, their misfolding may cause dysbiosis. However, whether ER stress, α-defensin misfolding, and dysbiosis contribute to the pathophysiology of CD remains unknown. Here, we show that abnormal Paneth cells with markers of ER stress appear in SAMP1/YitFc, a mouse model of CD, along with disease progression. Those mice secrete reduced-form α-defensins that lack disulfide bonds into the intestinal lumen, a condition not found in normal mice, and reduced-form α-defensins correlate with dysbiosis during disease progression. Moreover, administration of reduced-form α-defensins to wild-type mice induces the dysbiosis. These data provide novel insights into CD pathogenesis induced by dysbiosis resulting from Paneth cell α-defensin misfolding and they suggest further that Paneth cells may be potential therapeutic targets.

Identifiants

pubmed: 32345659
pii: 3/6/e201900592
doi: 10.26508/lsa.201900592
pmc: PMC7190275
pii:
doi:

Substances chimiques

RNA, Ribosomal, 16S 0
alpha-Defensins 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

© 2020 Shimizu et al.

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Auteurs

Yu Shimizu (Y)

Innate Immunity Laboratory, Graduate School of Life Science, Hokkaido University, Hokkaido, Japan.
Department of Cell Biological Science, Faculty of Advanced Life Science, Hokkaido University, Hokkaido, Japan.

Kiminori Nakamura (K)

Innate Immunity Laboratory, Graduate School of Life Science, Hokkaido University, Hokkaido, Japan.
Department of Cell Biological Science, Faculty of Advanced Life Science, Hokkaido University, Hokkaido, Japan.

Aki Yoshii (A)

Innate Immunity Laboratory, Graduate School of Life Science, Hokkaido University, Hokkaido, Japan.

Yuki Yokoi (Y)

Innate Immunity Laboratory, Graduate School of Life Science, Hokkaido University, Hokkaido, Japan.
Department of Cell Biological Science, Faculty of Advanced Life Science, Hokkaido University, Hokkaido, Japan.

Mani Kikuchi (M)

Department of Cell Biological Science, Faculty of Advanced Life Science, Hokkaido University, Hokkaido, Japan.

Ryuga Shinozaki (R)

Innate Immunity Laboratory, Graduate School of Life Science, Hokkaido University, Hokkaido, Japan.

Shunta Nakamura (S)

Innate Immunity Laboratory, Graduate School of Life Science, Hokkaido University, Hokkaido, Japan.

Shuya Ohira (S)

Innate Immunity Laboratory, Graduate School of Life Science, Hokkaido University, Hokkaido, Japan.

Rina Sugimoto (R)

Innate Immunity Laboratory, Graduate School of Life Science, Hokkaido University, Hokkaido, Japan.

Tokiyoshi Ayabe (T)

Innate Immunity Laboratory, Graduate School of Life Science, Hokkaido University, Hokkaido, Japan ayabe@sci.hokudai.ac.jp.
Department of Cell Biological Science, Faculty of Advanced Life Science, Hokkaido University, Hokkaido, Japan.

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