Id3调控新月体肾炎早期Th17和Treg细胞分化的机制研究

Crescentic glomerulonephritis （CGN）has a rapid onset and leads to rapidly progressive renal injury and poor prognosis. Th17 cell-mediated immune response mainly participates in the early stage of CGN, and regulatory T cells (Treg) alleviates the pathological damages by inhibiting T cell immune response. Th17 and Treg have the same precursor cells and have a lot of similarities in differentiation. Meanwhile, Treg can be transformed into Th17 under particular conditions. The pathogenesis of CGN can be clarified by investigating the regulation mechanisms of the differentiation between Th17 and Treg. DNA binding inhibition factor 3 (Id3) can regulate the expression of Th17 and Treg characteristic transcription factors (RORγt and Foxp3) at the transcriptional level. This project will study the regulation effect of Treg and Th17 differentiation in the early stage of CGN by using the gene regulation to change the expression of Id3. We further explore that whether Id3 regulates the differentiation of Th17 and Treg through the effect with transcription factor E2A to influence the transcription of RORγt and Foxp3 or not. We will study the mechanisms of Th17 and Treg differentiation in the early stage of CGN from the gene regulation, which contributes to the crucial factors in activation of the immune responses in CGN and provides the basis for early intervention in immune responses and the amelioration of pathological damages.

新月体肾炎(CGN)起病急骤，肾功能急剧恶化，预后差。早期以Th17细胞介导的免疫反应为主，调节性T细胞（Treg）则通过抑制T细胞免疫应答减轻病理损害；Th17和Treg具有共同的前体细胞，在分化上具有很多相似之处，并且在特定条件下Treg可转化为Th17。通过探讨CGN中Th17和Treg的分化调控机制，有助于阐明CGN的发病机理。DNA结合抑制因子3(Id3)可在转录水平调节Th17和Treg特征性转录因子(RORγt和Foxp3)的表达。本课题将利用基因调控技术，调节Id3的表达水平，研究其在CGN早期对Th17和Treg分化的调控作用；并进一步探讨Id3是否通过与转录因子E2A作用，影响RORγt和Foxp3转录，进而调控Th17和Treg分化。通过对CGN早期Th17和Treg分化机制的研究，探讨CGN免疫反应活化的关键因素，为早期干预免疫反应，减轻病理损害提供理论依据。

本课题通过建立新月体肾炎模型,利用RTPCR和Western blot从基因和蛋白两个水平明确了新月体肾炎效应期和诱导期Th17和Treg的分化过程与ID3及E2A表达密切相关;并试图利用基因调控技术，调节Id3的表达水平，从细胞水平探讨ID3的表达与Th17和Treg分化之间的关系，研究其在CGN早期对Th17和Treg分化的调控作用。通过对CGN早期Th17和Treg分化机制的研究，探讨CGN免疫反应活化的关键因素，为早期干预免疫反应，减轻病理损害提供理论依据。