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Интеллектуальная Система Тематического Исследования НАукометрических данных |
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Dendritic cells derived IL-6 protects from epithelial damage during colitis and drives colitis-associated cancer by controlling RORɣt+ cell accumulationтезисы доклада
- Авторы: Gubernatorova E.O., Polinova A.I., Gorshkova E.A., Drutskaya M.D., Nedospasov S.A.
- Сборник: European Journal of Immunology
- Том: 51
- Тезисы
- Год издания: 2021
- Издательство: Wiley & Sons
- Местоположение издательства: Chichester, Sussex, UK, England
- Первая страница: 238
- Последняя страница: 238
- Номер статьи: P-0514
- DOI: 10.1002/eji.202170200
- Аннотация: IL-6 is known for its ability to drive tumor progression in the gut and to support intestinal barrier functions during acute colitis. IL-6-deficient mice develop severe colon inflammation in dextran sodium sulfate (DSS)-induced colitis model, but demonstrate reduced tumor burden in azoxymethane (AOM)–DSS colitis-associated cancer. Accumulating evidence suggests that dendritic cell-derived IL-6 may represent the major regulator of IL-6-dependent processes during gut inflammation. To test this hypothesis we compared IL-6 knockout (KO) mice, mice with cell-specific ablation of IL-6 in CD11c+ cells, and wild type littermate control mice in the models of acute DSS-induced colitis, and AOM-DSS-induced colorectal cancer. We found that CD11c-IL-6 KO mice developed more severe intestinal inflammation with elevated expression levels of TGFβ and RegIIIɣ compared to wild type littermate control mice. In AOM-DSS model, CD11с-IL-6 KO, as well as IL-6 KO mice demonstrated lower tumor load than wild type littermate control mice. Interestingly, the frequency of both Th17 and Treg cells, dependent of the master transcriptional factor RORɣt, were decreased in inflamed colon and in tumors of IL-6 deficient mice. RORɣt+ cells are the key population controlling intestinal barrier function and homeostasis and their decrease with subsequent abrogation of IL-17 expression in the colon may represent the mechanism of enhanced tumor control.Taken together, our data suggest that IL-6 produced by dendritic cells may affect colon integrity during acute colitis and tumor progression in colitis-associated cancer model through activation of RORɣt cells in the gut.
- Добавил в систему: Полинова Альмина Игоревна