Regulatory T Cells Developing Peri-Weaning Are Continually Required to Restrain Th2 Systemic Responses Later in Life.
Regulatory T Cells Developing Peri-Weaning Are Continually Required to Restrain Th2 Systemic Responses Later in Life.
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DOI：
10.3389/fimmu.2020.603059
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发表时间：
2020
影响因子：
7.3
通讯作者：
Newberry RD
中科院分区：
文献类型：
--
作者：
Knoop KA;McDonald KG;Hsieh CS;Tarr PI;Newberry RD
包括过敏性鼻炎、哮喘、食物过敏和皮炎在内的特应性疾病在西方社会越来越普遍。这些疾病的主要特征是辅助性T细胞2型(Th2)对环境诱因，特别是吸入和饮食过敏原的免疫反应。在儿童早期接触这种刺激可以减少高危儿童过敏的频率。这些过敏反应可以被调节性T细胞(Tregs)抑制，特别是在肠道中出现的Tregs。早期生命如何接触饮食和微生物的独特属性塑造了肠道Treg种群，这是一个非常感兴趣的话题。虽然早期的印记促进了平衡的免疫系统的发展，并防止免疫病理，但尚不清楚在早期生命中形成的树突状细胞是否会在整个成年期继续抑制全身炎症反应。在这里，使用可诱导删除策略来标记特定时间点的Tregs，并有针对性地稍后删除。在出生24天，但不是在出生14天断奶之前，删除标记为围绝乳期的Treg，导致循环中IgE和IL-13增加，并取消对新抗原的耐受诱导。因此，发育在断奶期间，但不是在生命14天之前的树不断地被要求在成年后抑制过敏反应。
Atopic disorders including allergic rhinitis, asthma, food allergy, and dermatitis, are increasingly prevalent in Western societies. These disorders are largely characterized by T helper type 2 (Th2) immune responses to environmental triggers, particularly inhaled and dietary allergens. Exposure to such stimuli during early childhood reduces the frequency of allergies in at-risk children. These allergic responses can be restrained by regulatory T cells (Tregs), particularly Tregs arising in the gut. The unique attributes of how early life exposure to diet and microbes shape the intestinal Treg population is a topic of significant interest. While imprinting during early life promotes the development of a balanced immune system and protects against immunopathology, it remains unclear if Tregs that develop in early life continue to restrain systemic inflammatory responses throughout adulthood. Here, an inducible deletion strategy was used to label Tregs at specified time points with a targeted mechanism to be deleted later. Deletion of the Tregs labeled peri-weaning at day of life 24, but not before weaning at day of life 14, resulted in increased circulating IgE and IL-13, and abrogated induction of tolerance towards new antigens. Thus, Tregs developing peri-weaning, but not before day of life 14 are continually required to restrain allergic responses into adulthood.
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DOI：
10.1126/science.1198469
发表时间：
2011-01-21
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Atarashi K;Tanoue T;Shima T;Imaoka A;Kuwahara T;Momose Y;Cheng G;Yamasaki S;Saito T;Ohba Y;Taniguchi T;Takeda K;Hori S;Ivanov II;Umesaki Y;Itoh K;Honda K
通讯作者：
Honda K
影响因子：
24.8
作者：
Knoop KA;Gustafsson JK;McDonald KG;Kulkarni DH;Coughlin PE;McCrate S;Kim D;Hsieh CS;Hogan SP;Elson CO;Tarr PI;Newberry RD
通讯作者：
Newberry RD
影响因子：
48
作者：
Buch, T;Heppner, FL;Waisman, A
通讯作者：
Waisman, A
影响因子：
8
作者：
Knoop, Kathryn A.;McDonald, Keely G.;Newberry, Rodney D.
通讯作者：
Newberry, Rodney D.
影响因子：
82.9
作者：
Abdel-Gadir, Azza;Stephen-Victor, Emmanuel;Chatila, Talal A.
通讯作者：
Chatila, Talal A.