Nature medicine · 2023
Antigen-driven colonic inflammation is associated with development of dysplasia in primary sclerosing cholangitis.
СтатьяПоддержка NIH: внешняя программаПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
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Shaw Dustin G, Aguirre-Gamboa Raúl, Vieira Marcos C, Gona Saideep, DiNardi Nicholas, Wang Anni, Dumaine Anne, Gelderloos-Arends Jody, Earley Zachary M, Meckel Katherine R, Ciszewski Cezary, Castillo Anabella, Monroe Kelly, Torres Joana, Shah Shailja C, Colombel Jean-Frédéric, Itzkowitz Steven, Newberry Rodney, Cohen Russell D, Rubin David T, Quince Christopher, Cobey Sarah, Jonkers Iris H, Weber Christopher R, Pekow Joel, Wilson Patrick C, Barreiro Luis B, Jabri Bana
Аннотация
Primary sclerosing cholangitis (PSC) is an immune-mediated disease of the bile ducts that co-occurs with inflammatory bowel disease (IBD) in almost 90% of cases. Colorectal cancer is a major complication of patients with PSC and IBD, and these patients are at a much greater risk compared to patients with IBD without concomitant PSC. Combining flow cytometry, bulk and single-cell transcriptomics, and T and B cell receptor repertoire analysis of right colon tissue from 65 patients with PSC, 108 patients with IBD and 48 healthy individuals we identified a unique adaptive inflammatory transcriptional signature associated with greater risk and shorter time to dysplasia in patients with PSC. This inflammatory signature is characterized by antigen-driven interleukin-17A (IL-17A)+ forkhead box P3 (FOXP3)+ CD4 T cells that express a pathogenic IL-17 signature, as well as an expansion of IgG-secreting plasma cells. These results suggest that the mechanisms that drive the emergence of dysplasia in PSC and IBD are distinct and provide molecular insights that could guide prevention of colorectal cancer in individuals with PSC.