Loss of Adenosine Deaminase Acting on RNA 1 Induces Panoptosis and Immune Response in Ulcerative Colitis Gut Mucosa
ABSTRACT The gut virome is a complex community that exists in equilibrium with the host. Disruptions of this balance could drive the development of inflammatory diseases, such as inflammatory bowel disease (IBD). RNA editing, particularly A‐to‐I editing by ADAR1, prevents the excessive immune respon...
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2025-06-01
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| Online Access: | https://doi.org/10.1002/mco2.70212 |
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| author | Andrea Iannucci Marco Colella Macarena Quiroga Rachele Frascatani Lorenzo Tomassini Claudia Maresca Eleonora Franzè Federica Laudisi Giuseppe Sica Irene Marafini Alessandro Michienzi Ivan Zanoni Giovanni Monteleone Ivan Monteleone |
| author_facet | Andrea Iannucci Marco Colella Macarena Quiroga Rachele Frascatani Lorenzo Tomassini Claudia Maresca Eleonora Franzè Federica Laudisi Giuseppe Sica Irene Marafini Alessandro Michienzi Ivan Zanoni Giovanni Monteleone Ivan Monteleone |
| author_sort | Andrea Iannucci |
| collection | DOAJ |
| description | ABSTRACT The gut virome is a complex community that exists in equilibrium with the host. Disruptions of this balance could drive the development of inflammatory diseases, such as inflammatory bowel disease (IBD). RNA editing, particularly A‐to‐I editing by ADAR1, prevents the excessive immune response to viral double strand (ds) RNA. Failure of RNA editing may sustain inflammation and this study explore the role of ADAR1 in IBD. ADAR1 was analyzed in IBD patients and healthy controls (CTR) using western blotting and qPCR. Colonic epithelial cells (HCEC‐1CT), ex vivo organ cultures, and colonic organoids were treated poly I:C after ADAR1 silencing with an antisense oligonucleotide (AS). Inflammatory pathways and PANoptosome were measured by western blotting, flow cytometry, and ELISA. The role of ADAR1 was also studied in DSS‐colitis model. ADAR1 was significantly reduced in the inflamed epithelium of ulcerative colitis (UC) gut samples. ADAR1 silencing in HCEC‐1CT, ex vivo organ cultures or colonic organoids strongly increases the immune response to poly I:C and leads to activation of inflammatory pathways and PANoptosis. Inhibition of gut ADAR1 expression during DSS‐colitis exacerbated gut inflammation. JAK inhibition or AhR activation mitigated the immune response that follows ADAR1 silencing. These data suggest that ADAR1 could be involved in IBD inflammation. |
| format | Article |
| id | doaj-art-ac8f3567a28b40ac99610882c8c2d4d2 |
| institution | Kabale University |
| issn | 2688-2663 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Wiley |
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| series | MedComm |
| spelling | doaj-art-ac8f3567a28b40ac99610882c8c2d4d22025-08-20T03:39:28ZengWileyMedComm2688-26632025-06-0166n/an/a10.1002/mco2.70212Loss of Adenosine Deaminase Acting on RNA 1 Induces Panoptosis and Immune Response in Ulcerative Colitis Gut MucosaAndrea Iannucci0Marco Colella1Macarena Quiroga2Rachele Frascatani3Lorenzo Tomassini4Claudia Maresca5Eleonora Franzè6Federica Laudisi7Giuseppe Sica8Irene Marafini9Alessandro Michienzi10Ivan Zanoni11Giovanni Monteleone12Ivan Monteleone13Department of Biomedicine and Prevention University of Rome "Tor Vergata"Rome ItalyDepartment of Systems Medicine University of Rome "Tor Vergata"Rome ItalyEpithelial Plasticity and Metastasis GroupInstituto de Investigación Biomédica de A Coruña (INIBIC) Complexo Hospitalario Universitario de A Coruña (CHUAC)SergasUniversidade da Coruña (UDC)A CorunaSpainDepartment of Systems Medicine University of Rome "Tor Vergata"Rome ItalyDepartment of Systems Medicine University of Rome "Tor Vergata"Rome ItalyDepartment of Systems Medicine University of Rome "Tor Vergata"Rome ItalyDepartment of Systems Medicine University of Rome "Tor Vergata"Rome ItalyDepartment of Systems Medicine University of Rome "Tor Vergata"Rome ItalyDepartment of Surgery University of Rome "Tor Vergata"Rome ItalyAzienda Ospedaliera Policlinico Tor VergataRomeItalyDepartment of Biomedicine and Prevention University of Rome "Tor Vergata"Rome ItalyDivision of Immunology and Division of Gastroenterology Harvard Medical School and Boston Children's HospitalBostonMassachusetts USADepartment of Systems Medicine University of Rome "Tor Vergata"Rome ItalyDepartment of Biomedicine and Prevention University of Rome "Tor Vergata"Rome ItalyABSTRACT The gut virome is a complex community that exists in equilibrium with the host. Disruptions of this balance could drive the development of inflammatory diseases, such as inflammatory bowel disease (IBD). RNA editing, particularly A‐to‐I editing by ADAR1, prevents the excessive immune response to viral double strand (ds) RNA. Failure of RNA editing may sustain inflammation and this study explore the role of ADAR1 in IBD. ADAR1 was analyzed in IBD patients and healthy controls (CTR) using western blotting and qPCR. Colonic epithelial cells (HCEC‐1CT), ex vivo organ cultures, and colonic organoids were treated poly I:C after ADAR1 silencing with an antisense oligonucleotide (AS). Inflammatory pathways and PANoptosome were measured by western blotting, flow cytometry, and ELISA. The role of ADAR1 was also studied in DSS‐colitis model. ADAR1 was significantly reduced in the inflamed epithelium of ulcerative colitis (UC) gut samples. ADAR1 silencing in HCEC‐1CT, ex vivo organ cultures or colonic organoids strongly increases the immune response to poly I:C and leads to activation of inflammatory pathways and PANoptosis. Inhibition of gut ADAR1 expression during DSS‐colitis exacerbated gut inflammation. JAK inhibition or AhR activation mitigated the immune response that follows ADAR1 silencing. These data suggest that ADAR1 could be involved in IBD inflammation.https://doi.org/10.1002/mco2.70212adenosine deaminase acting on RNA 1inflammatory bowel diseaseinnate immunitymucosal damagepanoptosis |
| spellingShingle | Andrea Iannucci Marco Colella Macarena Quiroga Rachele Frascatani Lorenzo Tomassini Claudia Maresca Eleonora Franzè Federica Laudisi Giuseppe Sica Irene Marafini Alessandro Michienzi Ivan Zanoni Giovanni Monteleone Ivan Monteleone Loss of Adenosine Deaminase Acting on RNA 1 Induces Panoptosis and Immune Response in Ulcerative Colitis Gut Mucosa MedComm adenosine deaminase acting on RNA 1 inflammatory bowel disease innate immunity mucosal damage panoptosis |
| title | Loss of Adenosine Deaminase Acting on RNA 1 Induces Panoptosis and Immune Response in Ulcerative Colitis Gut Mucosa |
| title_full | Loss of Adenosine Deaminase Acting on RNA 1 Induces Panoptosis and Immune Response in Ulcerative Colitis Gut Mucosa |
| title_fullStr | Loss of Adenosine Deaminase Acting on RNA 1 Induces Panoptosis and Immune Response in Ulcerative Colitis Gut Mucosa |
| title_full_unstemmed | Loss of Adenosine Deaminase Acting on RNA 1 Induces Panoptosis and Immune Response in Ulcerative Colitis Gut Mucosa |
| title_short | Loss of Adenosine Deaminase Acting on RNA 1 Induces Panoptosis and Immune Response in Ulcerative Colitis Gut Mucosa |
| title_sort | loss of adenosine deaminase acting on rna 1 induces panoptosis and immune response in ulcerative colitis gut mucosa |
| topic | adenosine deaminase acting on RNA 1 inflammatory bowel disease innate immunity mucosal damage panoptosis |
| url | https://doi.org/10.1002/mco2.70212 |
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