CD4的能力 T細胞分化為Th1和Th17或保護性調(diào)節(jié)性T細胞在自身免疫性疾病的發(fā)病機制中起著重要的作用 。最近的數(shù)據(jù)表明，CD4 T細胞亞群顯示相當(dāng)大的可塑性。這種可塑性似乎是其致病的關(guān)鍵因素，但也 過渡致病效應(yīng)T細胞向更耐受性的潛力。
當(dāng)前 研究的目的是分析在急性腎炎小鼠模型和小鼠狼瘡性腎炎慢性 模型Th17細胞的可塑性。通過將體外產(chǎn)生的，高度純化的Th17細胞并利用IL-17A命運記者 小鼠，我們表明，Th17細胞無法獲取的Th1和Th2細胞因子IFN-γγ簽名和 IL-13，分別大量表達，或T調(diào)節(jié)轉(zhuǎn)錄因子Foxp3在腎臟炎癥過程。為了打破 治療急性腎小球腎炎的Th17細胞表型穩(wěn)定，我們對腎病小鼠CD3特異 AB處理。事實上，這種治療誘導(dǎo)Th17細胞的免疫表型，這是由高 IL-10表達明顯減弱急性腎炎腎組織損傷。綜上所述，我們發(fā)現(xiàn)Th17細胞顯示最低 在急性和慢性實驗性腎小球腎炎的可塑性和引入抗CD3單抗作為一種工具來誘導(dǎo)的腎可以治療利用 調(diào)節(jié)Th17細胞表型。
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原文：
The ability of CD4+ T cells to differentiate into pathogenic Th1 and Th17 or protective T regulatory cells plays a pivotal role in the pathogenesis of autoimmune diseases. Recent data suggest that CD4+ T cell subsets display a considerable plasticity. This plasticity seems to be a critical factor for their pathogenicity, but also for the potential transition of pathogenic effector T cells toward a more tolerogenic phenotype. The aim of the current study was to analyze the plasticity of Th17 cells in a mouse model of acute crescentic glomerulonephritis and in a mouse chronic model of lupus nephritis. By transferring in vitro generated, highly purified Th17 cells and by using IL-17A fate reporter mice, we demonstrate that Th17 cells fail to acquire substantial expression of the Th1 and Th2 signature cytokines IFN-γ and IL-13, respectively, or the T regulatory transcription factor Foxp3 throughout the course of renal inflammation. In an attempt to therapeutically break the stability of the Th17 phenotype in acute glomerulonephritis, we subjected nephritic mice to CD3-specific Ab treatment. Indeed, this treatment induced an immunoregulatory phenotype in Th17 cells, which was marked by high expression of IL-10 and attenuated renal tissue damage in acute glomerulonephritis. In summary, we show that Th17 cells display a minimum of plasticity in acute and chronic experimental glomerulonephritis and introduce anti-CD3 treatment as a tool to induce a regulatory phenotype in Th17 cells in the kidney that may be therapeutically exploited.
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