EFHD2 suppresses intestinal inflammation by blocking intestinal epithelial cell TNFR1 internalization and cell death
© 2024. The Author(s)..
TNF acts as one pathogenic driver for inducing intestinal epithelial cell (IEC) death and substantial intestinal inflammation. How the IEC death is regulated to physiologically prevent intestinal inflammation needs further investigation. Here, we report that EF-hand domain-containing protein D2 (EFHD2), highly expressed in normal intestine tissues but decreased in intestinal biopsy samples of ulcerative colitis patients, protects intestinal epithelium from TNF-induced IEC apoptosis. EFHD2 inhibits TNF-induced apoptosis in primary IECs and intestinal organoids (enteroids). Mice deficient of Efhd2 in IECs exhibit excessive IEC death and exacerbated experimental colitis. Mechanistically, EFHD2 interacts with Cofilin and suppresses Cofilin phosphorylation, thus blocking TNF receptor I (TNFR1) internalization to inhibit IEC apoptosis and consequently protecting intestine from inflammation. Our findings deepen the understanding of EFHD2 as the key regulator of membrane receptor trafficking, providing insight into death receptor signals and autoinflammatory diseases.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:15 |
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| Enthalten in: |
Nature communications - 15(2024), 1 vom: 12. Feb., Seite 1282 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Wu, Jiacheng [VerfasserIn] |
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| Links: |
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| Themen: |
Actin Depolymerizing Factors |
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| Anmerkungen: |
Date Completed 14.02.2024 Date Revised 20.02.2024 published: Electronic Citation Status MEDLINE |
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| doi: |
10.1038/s41467-024-45539-x |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM368370909 |
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| 520 | |a © 2024. The Author(s). | ||
| 520 | |a TNF acts as one pathogenic driver for inducing intestinal epithelial cell (IEC) death and substantial intestinal inflammation. How the IEC death is regulated to physiologically prevent intestinal inflammation needs further investigation. Here, we report that EF-hand domain-containing protein D2 (EFHD2), highly expressed in normal intestine tissues but decreased in intestinal biopsy samples of ulcerative colitis patients, protects intestinal epithelium from TNF-induced IEC apoptosis. EFHD2 inhibits TNF-induced apoptosis in primary IECs and intestinal organoids (enteroids). Mice deficient of Efhd2 in IECs exhibit excessive IEC death and exacerbated experimental colitis. Mechanistically, EFHD2 interacts with Cofilin and suppresses Cofilin phosphorylation, thus blocking TNF receptor I (TNFR1) internalization to inhibit IEC apoptosis and consequently protecting intestine from inflammation. Our findings deepen the understanding of EFHD2 as the key regulator of membrane receptor trafficking, providing insight into death receptor signals and autoinflammatory diseases | ||
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| 700 | 1 | |a Duan, Jiaqi |e verfasserin |4 aut | |
| 700 | 1 | |a Chai, Yangyang |e verfasserin |4 aut | |
| 700 | 1 | |a Song, Jiaying |e verfasserin |4 aut | |
| 700 | 1 | |a Gong, Dongsheng |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Bingjing |e verfasserin |4 aut | |
| 700 | 1 | |a Hu, Ye |e verfasserin |4 aut | |
| 700 | 1 | |a Han, Taotao |e verfasserin |4 aut | |
| 700 | 1 | |a Ding, Yuanyuan |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Yin |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Jingnan |e verfasserin |4 aut | |
| 700 | 1 | |a Cao, Xuetao |e verfasserin |4 aut | |
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