Life sciences · 2025
Akkermansia muciniphila restrains type 1 diabetes onset by eliciting cDC2 and Treg cell differentiation in NOD and STZ-induced experimental models.
СтатьяНазвание и аннотация: Перевод пока не подготовлен
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Rodrigues Vanessa Fernandes, Elias-Oliveira Jefferson, Pereira Ítalo Sousa, Pereira Jéssica Assis, Barbosa Sara Cândida, Machado Melissa Santana Gonsalez, Guimarães Jhefferson Barbosa, Pacheco Thaílla Cristina Faria, Bortolucci Jonatã, Zaramela Lívia Soares, Bonato Vânia Luiza Deperon, Silva João Santana, Martins Flaviano Santos, Alves-Filho José Carlos, Gardinassi Luiz Gustavo, Reginatto Valeria, Carlos Daniela
Аннотация
AIMS: Akkermansia muciniphila (A. muciniphila), a Gram-negative anaerobic mucus-layer-degrading bacterium found in the intestinal mucosa, exhibits potential as a probiotic, showing promise in mitigating autoimmune and chronic inflammatory diseases. This study aims to investigate whether A. muciniphila supplementation might confer protection against type 1 diabetes (T1D) and to elucidate the immunological pathways through which it exerts its beneficial effects.
MATERIALS AND METHODS: Non-obese diabetic (NOD) mice and streptozotocin (STZ)-induced type 1 diabetes (T1D) models were used to evaluate the protective effects of A. muciniphila during T1D course. Body weight, blood glucose levels, and T1D incidence were monitored. Immune responses in the pancreas, pancreatic (PLN) and cecal lymph nodes (CLN) and bone marrow-derived dendritic cells (BMDC) were evaluated by flow cytometry and ELISA.
KEY FINDINGS: Viable A. muciniphila supplementation conferred protection against T1D onset in STZ-induced T1D and NOD mouse models. T1D modulation by A. muciniphila in the STZ model was independent of the gut microbiota, and it was associated with increased tolerogenic type-2 dendritic cells (SIRP-α+CD11b+CD103+) and regulatory T (Treg) cells in PLN and pancreas. BMDC differentiated in the presence of A. muciniphila exhibited a tolerogenic profile and induced Treg cell generation in vitro. A. muciniphila-induced protection in T1D outcome was abrogated in FOXP3-DTR mice depleted of Treg cells, indicating that its mechanism of action is dependent on the CD4+Foxp3+ Treg cells.
SIGNIFICANCE: A. muciniphila supplementation attenuates T1D development in mice by modulating the tolerogenic immune response and is a promising new therapeutic tool for this autoimmune disease.
MATERIALS AND METHODS: Non-obese diabetic (NOD) mice and streptozotocin (STZ)-induced type 1 diabetes (T1D) models were used to evaluate the protective effects of A. muciniphila during T1D course. Body weight, blood glucose levels, and T1D incidence were monitored. Immune responses in the pancreas, pancreatic (PLN) and cecal lymph nodes (CLN) and bone marrow-derived dendritic cells (BMDC) were evaluated by flow cytometry and ELISA.
KEY FINDINGS: Viable A. muciniphila supplementation conferred protection against T1D onset in STZ-induced T1D and NOD mouse models. T1D modulation by A. muciniphila in the STZ model was independent of the gut microbiota, and it was associated with increased tolerogenic type-2 dendritic cells (SIRP-α+CD11b+CD103+) and regulatory T (Treg) cells in PLN and pancreas. BMDC differentiated in the presence of A. muciniphila exhibited a tolerogenic profile and induced Treg cell generation in vitro. A. muciniphila-induced protection in T1D outcome was abrogated in FOXP3-DTR mice depleted of Treg cells, indicating that its mechanism of action is dependent on the CD4+Foxp3+ Treg cells.
SIGNIFICANCE: A. muciniphila supplementation attenuates T1D development in mice by modulating the tolerogenic immune response and is a promising new therapeutic tool for this autoimmune disease.