Role of BCL-6 in Allergic Immune Responses

描述(申请人提供)：转录抑制蛋白BCL6 与非霍奇金？S淋巴瘤的发病机制有关，但很少 已知BCL6的正常功能。我们之前已经表明， 靶向破坏BCL6基因会导致Th2介导的炎症， 提示BCL6在调节辅助性T细胞亚型中起重要作用 2(Th2)亚群分化。细胞因子IL-4与转录因子 STAT6是Th2分化的重要调节因子。我们发现BCL6 调节一种不依赖IL-4的Th2分化新途径 和STAT6。我们的假设是，细胞因子IL-6具有独特的能力 通过IL-4/STAT6非依赖性途径诱导Th2分化。在这 建议，我们计划使用小鼠遗传、细胞和分子技术来 BCL6调控Th2细胞这一新途径的机制研究 差异化。这些研究将为正常的Th2提供重要的见解 辨证，这可能导致对过敏性疾病的新理解，如 作为哮喘。这些研究还将提供对BCL6功能的洞察， 这可能有助于B细胞淋巴瘤的治疗。

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.