<i>C. elegans</i> Hemidesmosomes Sense Collagen Damage to Trigger Innate Immune Response in the Epidermis
The collagens are an enormous family of extracellular matrix proteins that play dominant roles in cell adhesion, migration and tissue remodeling under many physiological and pathological conditions. However, their function mechanisms in regulating innate immunity remain largely undiscovered. Here we...
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MDPI AG
2023-09-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/12/18/2223 |
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| author | Yi Zhu Wenna Li Yifang Dong Chujie Xia Rong Fu |
| author_facet | Yi Zhu Wenna Li Yifang Dong Chujie Xia Rong Fu |
| author_sort | Yi Zhu |
| collection | DOAJ |
| description | The collagens are an enormous family of extracellular matrix proteins that play dominant roles in cell adhesion, migration and tissue remodeling under many physiological and pathological conditions. However, their function mechanisms in regulating innate immunity remain largely undiscovered. Here we use <i>C. elegans</i> epidermis as the model to address this question. The <i>C. elegans</i> epidermis is covered with a collagen-rich cuticle exoskeleton and can produce antimicrobial peptides (AMPs) against invading pathogens or physical injury. Through an RNAi screen against collagen-encoding genes, we found that except the previously reported six DPY collagens and the BLI-1 collagen, the majority of collagens tested appear unable to trigger epidermal immune defense when damaged. Further investigation suggests that the six DPY collagens form a specific substructure, which regulates the interaction between BLI-1 and the hemidesmosome receptor MUP-4. The separation of BLI-1 with MUP-4 caused by collagen damage leads to the detachment of the STAT transcription factor-like protein STA-2 from hemidesmosomes and the induction of AMPs. Our findings uncover the mechanism how collagens are organized into a damage sensor and how the epidermis senses collagen damage to mount an immune defense. |
| first_indexed | 2024-03-10T22:56:18Z |
| format | Article |
| id | doaj.art-73aa5e64930a46c6bea83859ed856e82 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T22:56:18Z |
| publishDate | 2023-09-01 |
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| series | Cells |
| spelling | doaj.art-73aa5e64930a46c6bea83859ed856e822023-11-19T09:59:01ZengMDPI AGCells2073-44092023-09-011218222310.3390/cells12182223<i>C. elegans</i> Hemidesmosomes Sense Collagen Damage to Trigger Innate Immune Response in the EpidermisYi Zhu0Wenna Li1Yifang Dong2Chujie Xia3Rong Fu4Jiangsu Key Laboratory of Infection and Immunity, Institutes of Biology and Medical Sciences, Soochow University, Suzhou 215123, ChinaJiangsu Key Laboratory of Infection and Immunity, Institutes of Biology and Medical Sciences, Soochow University, Suzhou 215123, ChinaJiangsu Key Laboratory of Infection and Immunity, Institutes of Biology and Medical Sciences, Soochow University, Suzhou 215123, ChinaJiangsu Key Laboratory of Infection and Immunity, Institutes of Biology and Medical Sciences, Soochow University, Suzhou 215123, ChinaJiangsu Key Laboratory of Infection and Immunity, Institutes of Biology and Medical Sciences, Soochow University, Suzhou 215123, ChinaThe collagens are an enormous family of extracellular matrix proteins that play dominant roles in cell adhesion, migration and tissue remodeling under many physiological and pathological conditions. However, their function mechanisms in regulating innate immunity remain largely undiscovered. Here we use <i>C. elegans</i> epidermis as the model to address this question. The <i>C. elegans</i> epidermis is covered with a collagen-rich cuticle exoskeleton and can produce antimicrobial peptides (AMPs) against invading pathogens or physical injury. Through an RNAi screen against collagen-encoding genes, we found that except the previously reported six DPY collagens and the BLI-1 collagen, the majority of collagens tested appear unable to trigger epidermal immune defense when damaged. Further investigation suggests that the six DPY collagens form a specific substructure, which regulates the interaction between BLI-1 and the hemidesmosome receptor MUP-4. The separation of BLI-1 with MUP-4 caused by collagen damage leads to the detachment of the STAT transcription factor-like protein STA-2 from hemidesmosomes and the induction of AMPs. Our findings uncover the mechanism how collagens are organized into a damage sensor and how the epidermis senses collagen damage to mount an immune defense.https://www.mdpi.com/2073-4409/12/18/2223epidermisinnate immunitycollagenhemidesmosomeantimicrobial peptide |
| spellingShingle | Yi Zhu Wenna Li Yifang Dong Chujie Xia Rong Fu <i>C. elegans</i> Hemidesmosomes Sense Collagen Damage to Trigger Innate Immune Response in the Epidermis Cells epidermis innate immunity collagen hemidesmosome antimicrobial peptide |
| title | <i>C. elegans</i> Hemidesmosomes Sense Collagen Damage to Trigger Innate Immune Response in the Epidermis |
| title_full | <i>C. elegans</i> Hemidesmosomes Sense Collagen Damage to Trigger Innate Immune Response in the Epidermis |
| title_fullStr | <i>C. elegans</i> Hemidesmosomes Sense Collagen Damage to Trigger Innate Immune Response in the Epidermis |
| title_full_unstemmed | <i>C. elegans</i> Hemidesmosomes Sense Collagen Damage to Trigger Innate Immune Response in the Epidermis |
| title_short | <i>C. elegans</i> Hemidesmosomes Sense Collagen Damage to Trigger Innate Immune Response in the Epidermis |
| title_sort | i c elegans i hemidesmosomes sense collagen damage to trigger innate immune response in the epidermis |
| topic | epidermis innate immunity collagen hemidesmosome antimicrobial peptide |
| url | https://www.mdpi.com/2073-4409/12/18/2223 |
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