Intestinal microbial diversity during early-life colonization shapes long-term IgE levels.
Intestinal microbial diversity during early-life colonization shapes long-term IgE levels.
复制标题
DOI：
10.1016/j.chom.2013.10.004
复制
发表时间：
2013-11-13
影响因子：
30.3
通讯作者：
McCoy KD
中科院分区：
文献类型：
--
作者：
Cahenzli J;Köller Y;Wyss M;Geuking MB;McCoy KD
出生后接触微生物会对哺乳动物的免疫系统发育产生深远影响。微生物群的改变与过敏性和自身免疫性疾病的发病率增加有关，血清IgE升高是一个标志。先前报道的无菌小鼠血清中异常高的IgE水平表明，来自微生物群的免疫调节信号是控制基础IgE水平所必需的。我们报道无菌小鼠和微生物群多样性低的小鼠在生命早期血清IgE水平升高。新生无菌小鼠的B细胞在粘膜部位以CD4 t细胞和il -4依赖的方式向IgE进行同型转换。为了抑制IgE诱导，出生后的微生物多样性需要达到一个临界水平。无菌小鼠的IgE水平升高导致肥大细胞表面结合的IgE增加和口服诱导的全身过敏反应加重。因此，生命早期适当的肠道微生物刺激对于诱导免疫调节网络至关重要，该网络可保护粘膜部位免受IgE的诱导。无菌小鼠和微生物群多样性低的小鼠血清IgE水平较高，无菌小鼠的B细胞在粘膜部位进行IgE类开关重组，生命早期需要多样化的微生物群来抑制IgE诱导，无菌小鼠的高IgE会导致严重的口服诱导全身过敏反应
Microbial exposure following birth profoundly impacts mammalian immune system development. Microbiota alterations are associated with increased incidence of allergic and autoimmune disorders with elevated serum IgE as a hallmark. The previously reported abnormally high serum IgE levels in germ-free mice suggests that immunoregulatory signals from microbiota are required to control basal IgE levels. We report that germ-free mice and those with low-diversity microbiota develop elevated serum IgE levels in early life. B cells in neonatal germ-free mice undergo isotype switching to IgE at mucosal sites in a CD4 T-cell- and IL-4-dependent manner. A critical level of microbial diversity following birth is required in order to inhibit IgE induction. Elevated IgE levels in germ-free mice lead to increased mast-cell-surface-bound IgE and exaggerated oral-induced systemic anaphylaxis. Thus, appropriate intestinal microbial stimuli during early life are critical for inducing an immunoregulatory network that protects from induction of IgE at mucosal sites. Germ-free and mice with low-diversity microbiota develop high serum IgE levels B cells in germ-free mice undergo IgE class switch recombination at mucosal sites A diverse microbiota early in life is required to inhibit IgE induction Hyper IgE in germ-free mice leads to exaggerated oral-induced systemic anaphylaxis
登录
查看更多内容
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：
32.4
作者：
Ganal, Stephanie C.;Sanos, Stephanie L.;Diefenbach, Andreas
通讯作者：
Diefenbach, Andreas
影响因子：
6.7
作者：
Endt K;Stecher B;Chaffron S;Slack E;Tchitchek N;Benecke A;Van Maele L;Sirard JC;Mueller AJ;Heikenwalder M;Macpherson AJ;Strugnell R;von Mering C;Hardt WD
通讯作者：
Hardt WD
影响因子：
10.4
作者：
Holt, PG
通讯作者：
Holt, PG
影响因子：
64.5
作者：
Garrett, Wendy S.;Lord, Graham M.;Glimcher, Laurie H.
通讯作者：
Glimcher, Laurie H.