Role of BCL-6 in Allergic Immune Responses

描述（由申请人提供）：转录抑制蛋白BCL 6 与非霍奇金淋巴瘤的发病机制有关s淋巴瘤，但很少 关于BCL 6的正常功能是已知的。我们之前已经证明， BCL 6基因的靶向破坏导致Th 2介导的炎症， 提示BCL 6在调节T辅助细胞类型中起重要作用， 2（Th 2）亚群分化。细胞因子IL-4和转录因子 STAT 6是Th 2分化的关键介质。我们发现BCL 6 调节不依赖于IL-4的Th 2分化的新途径 和STAT 6。我们的假设是，细胞因子IL-6具有独特的能力， 通过这种IL-4/STAT 6非依赖性途径诱导Th 2分化。在这 我们计划利用小鼠遗传、细胞和分子技术， 研究BCL 6调节Th 2这一新途径的机制 分化这些研究将为了解正常Th 2 分化，这可能导致对过敏性疾病的新认识， 哮喘。这些研究还将深入了解BCL 6的功能， 这可能有助于治疗B细胞淋巴瘤。

DESCRIPTION (provided by applicant): The transcriptional repressor protein BCL6 has been implicated in the pathogenesis of non-Hodgkin?s lymphoma, but little is known about the normal function of BCL6. We have previously shown that the targeted disruption of the BCL6 gene leads to Th2-mediated inflammation, suggesting that BCL6 plays an important role in the regulation of T helper type 2 (Th2) subset differentiation. The cytokine IL-4 and the transcription factor STAT6 are critical mediators of Th2 differentiation. We have found that BCL6 regulates a novel pathway of Th2 differentiation that is independent of IL-4 and STAT6. Our hypothesis is that the cytokine IL-6 has a unique ability to induce Th2 differentiation via this IL-4/STAT6-independent pathway. In this proposal, we plan to use mouse genetic, cellular and molecular techniques to study the mechanisms by which BCL6 regulates this novel pathway of Th2 differentiation. These studies will provide important insights into normal Th2 differentiation, which may lead to new understanding of allergic diseases such as asthma. These studies will also provide insight into the function of BCL6, which may help the treatment of B cell lymphoma.