PI3K is a negative regulator of IgE production
PI3K is a negative regulator of IgE production
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DOI：
10.1093/intimm/dxn009
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发表时间：
2008-04-01
影响因子：
4.4
通讯作者：
Koyasu, Shigeo
中科院分区：
文献类型：
--
作者：
Doi, Tomomitsu;Obayashi, Kunie;Koyasu, Shigeo
IgE是过敏性疾病如哮喘和特应性皮炎的主要参与者，其产生受到严格调节，并且IgE的血清浓度通常保持在比其他同种型低得多的水平。我们发现，缺乏p85 α调节亚基IA类磷脂酰肌醇3-激酶（PI 3 K）的小鼠产生的血清IgE的量增加。纯化的p85 α（-/-）B细胞在体外对抗CD 40 mAb和IL-4产生比野生型B细胞更多的IgE。PI 3 K抑制剂wortmannin和IC 87114增强了用抗CD 40 mAb和IL-4刺激的野生型B细胞的IgE产生。在相同条件下，抗原受体交联诱导分化抑制因子-2的表达，并以PI 3 K依赖的方式抑制活化诱导的胞苷脱氨酶和类别转换重组（CSR）的表达。IgE的产生也被抑制在浓缩的细胞培养条件下，这是完全逆转的PI 3 K抑制。在CSR后的蛋白质水平上也观察到PI 3 K对IgE产生的选择性抑制。我们的研究结果表明，PI 3 K负调节IgE的生产在CSR和蛋白质水平。
The production of IgE, a main player in allergic disorders such as asthma and atopic dermatitis, is strictly regulated and the serum concentrations of IgE are normally kept at a much lower level than other isotypes. We found that mice deficient for the p85 alpha regulatory subunit of class IA phosphoinositide 3-kinase (PI3K) produced increasing amounts of serum IgE. Purified p85 alpha(-/-) B cells produced more IgE than wild-type B cells in vitro in response to anti-CD40 mAb and IL-4. PI3K inhibitors wortmannin and IC87114 enhanced IgE production by wild-type B cells stimulated with anti-CD40 mAb and IL-4. Under the same condition, antigen receptor cross-linking induced the expression of inhibitor of differentiation-2 and suppressed the expression of activation-induced cytidine deaminase and class switch recombination (CSR) in a PI3K-dependent manner. IgE production was also suppressed in a concentrated cell culture condition, which was completely reversed by PI3K inhibition. The selective suppression of IgE production by PI3K was also observed at a protein level after CSR. Our results indicate that PI3K negatively regulates IgE production at both CSR and protein levels.