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A subset of patients with MIS-C were found to harbour rare variants in the gene BTNL8 that disrupt BTNL8-BTNL3 heterodimer formation, likely leading to inadequate \u03b3\u03b4 T-cell regulation and subsequent disrupted gut homeostasis. MIS-C shares clinical features with Kawasaki disease and similar mechanisms of pathogenesis with inflammatory bowel disease, despite these diseases being clinically distinct entities. We explore the common link between these diseases: the potentially critical role gut immunity plays in the initiation and persistence of disease through the tight regulation of \u03b3\u03b4 T cells via BTNL8 and BTNL3. Understanding the role of BTNL8 in the context of the overlap between these conditions may aid preventative measures and treatment of these conditions.<\/jats:p>","DOI":"10.1242\/dmm.052439","type":"journal-article","created":{"date-parts":[[2025,9,18]],"date-time":"2025-09-18T11:46:17Z","timestamp":1758195977000},"source":"Crossref","is-referenced-by-count":2,"title":["Unravelling \u03b3\u03b4 T-cell dysregulation in the gut and its implications for immune-mediated diseases"],"prefix":"10.1242","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-3966-4952","authenticated-orcid":false,"given":"Dilys","family":"Santillo","sequence":"first","affiliation":[{"name":"Imperial College London 1 Section of Paediatric Infectious Disease, Department of Infectious Disease, Faculty of Medicine , SW7 2AZ, London ,","place":["UK"]},{"name":"Centre for Paediatrics and Child Health 2 , Faculty of Medicine , , London SW7 2AZ ,","place":["UK"]},{"name":"Imperial College London 2 , Faculty of Medicine , , London SW7 2AZ ,","place":["UK"]},{"name":"Imperial College London 3 Section of Virology, Department of Infectious Disease, Faculty of Medicine , , London SW7 2AZ ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evangelos","family":"Bellos","sequence":"additional","affiliation":[{"name":"Imperial College London 1 Section of Paediatric Infectious Disease, Department of Infectious Disease, Faculty of Medicine , SW7 2AZ, London ,","place":["UK"]},{"name":"Centre for Paediatrics and Child Health 2 , Faculty of Medicine , , London SW7 2AZ ,","place":["UK"]},{"name":"Imperial College London 2 , Faculty of Medicine , , London SW7 2AZ ,","place":["UK"]},{"name":"University of Southampton 4 Human Genetics and Genomic Medicine, Faculty of Medicine , , Southampton SO16 6YD ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3519-0727","authenticated-orcid":false,"given":"Vanessa","family":"Sancho-Shimizu","sequence":"additional","affiliation":[{"name":"Imperial College London 1 Section of Paediatric Infectious Disease, Department of Infectious Disease, Faculty of Medicine , SW7 2AZ, London ,","place":["UK"]},{"name":"Centre for Paediatrics and Child Health 2 , Faculty of Medicine , , London SW7 2AZ ,","place":["UK"]},{"name":"Imperial College London 2 , Faculty of Medicine , , London SW7 2AZ ,","place":["UK"]},{"name":"Imperial College London 3 Section of Virology, Department of Infectious Disease, Faculty of Medicine , , London SW7 2AZ ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2025,9,18]]},"reference":[{"key":"2025101111014770100_DMM052439C1","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1186\/1471-2156-14-61","article-title":"A common 56-kilobase deletion in a primate-specific segmental duplication creates a novel butyrophilin-like protein","volume":"14","author":"Aigner","year":"2013","journal-title":"BMC Genet."},{"key":"2025101111014770100_DMM052439C2","doi-asserted-by":"publisher","first-page":"302","DOI":"10.1007\/s11894-012-0302-4","article-title":"Environmental triggers for inflammatory bowel disease","volume":"15","author":"Ananthakrishnan","year":"2013","journal-title":"Curr. 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