Bifidobacterium can mitigate intestinal immunopathology in the context of CTLA-4 blockade
Bifidobacterium can mitigate intestinal immunopathology in the context of CTLA-4 blockade
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DOI：
10.1073/pnas.1712901115
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发表时间：
2018-01-02
影响因子：
11.1
通讯作者：
Davis, Mark M.
中科院分区：
文献类型：
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作者：
Wang, Feng;Yin, Qian;Davis, Mark M.
削弱免疫耐受的抗体已被用于有效治疗癌症，但它们也会引发严重的自身免疫。为了研究这一点，我们将抗ctla -4治疗与标准结肠炎模型相结合，给予小鼠更严重的疾病形式。使用抗生素万古霉素进行预处理，引发了更严重的，基本上是致命的形式，这表明微生物群的革兰氏阳性成分具有缓解作用。然后我们发现，一种常用的益生菌双歧杆菌可以在很大程度上拯救小鼠的免疫病理，而对抗肿瘤免疫没有明显的影响，这种作用可能依赖于调节性T细胞。
Antibodies that attenuate immune tolerance have been used to effectively treat cancer, but they can also trigger severe autoimmunity. To investigate this, we combined anti-CTLA-4 treatment with a standard colitis model to give mice a more severe form of the disease. Pretreatment with an antibiotic, vancomycin, provoked an even more severe, largely fatal form, suggesting that a Gram-positive component of the microbiota had a mitigating effect. We then found that a commonly used probiotic, Bifidobacterium, could largely rescue the mice from immunopathology without an apparent effect on antitumor immunity, and this effect may be dependent on regulatory T cells.