Microbiota therapy acts via a regulatory T cell MyD88/RORγt pathway to suppress food allergy
Microbiota therapy acts via a regulatory T cell MyD88/RORγt pathway to suppress food allergy
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DOI：
10.1038/s41591-019-0461-z
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发表时间：
2019-07-01
期刊：
影响因子：
82.9
通讯作者：
Chatila, Talal A.
中科院分区：
文献类型：
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作者：
Abdel-Gadir, Azza;Stephen-Victor, Emmanuel;Chatila, Talal A.
生物失调在食物过敏(FA)中的作用尚不清楚。我们发现FA婴儿的非生物粪便微生物区系随着时间的推移而成分进化，并且未能保护小鼠免受FA的侵害。患有FA的婴儿和小鼠的IgA降低，与粪便细菌结合的IgE增加，这表明口服耐受性比迄今认识到的更广泛的崩溃。对受生物失调影响的梭状芽胞杆菌的治疗，无论是作为一个联合体，还是作为一个单一的变态杆菌治疗，都抑制了小鼠的FA，一个单独的免疫调节类杆菌联合体也是如此。细菌治疗通过调节性T(Treg)细胞以MyD88依赖的方式诱导转录因子ROR-Gamma t的表达，这种表达在FA婴儿和小鼠中是缺乏的，并且不能有效地被他们的微生物区系诱导。在Treg细胞中MyD88或RORC的缺失消除了细菌治疗的保护作用。因此，共生体激活新生Treg细胞中的MyD88/ROR-Gamma t通路以保护其免受FA的侵袭，而生物失调则削弱了这种促进疾病的调节反应。
The role of dysbiosis in food allergy (FA) remains unclear. We found that dysbiotic fecal microbiota in FA infants evolved compositionally over time and failed to protect against FA in mice. Infants and mice with FA had decreased IgA and increased IgE binding to fecal bacteria, indicative of a broader breakdown of oral tolerance than hitherto appreciated. Therapy with Clostridiales species impacted by dysbiosis, either as a consortium or as monotherapy with Subdoligranulum variabile, suppressed FA in mice as did a separate immunomodulatory Bacteroidales consortium. Bacteriotherapy induced expression by regulatory T (Treg) cells of the transcription factor ROR-gamma t in a MyD88-dependent manner, which was deficient in FA infants and mice and ineffectively induced by their microbiota. Deletion of Myd88 or Rorc in Treg cells abrogated protection by bacteriotherapy. Thus, commensals activate a MyD88/ROR-gamma t pathway in nascent Treg cells to protect against FA, while dysbiosis impairs this regulatory response to promote disease.