急性移植物抗宿主病(aGVHD)是异基因造血干细胞移植（HSCT）的主要并发症。新近发现调节性γδT(γδTreg)细胞具有免疫调控作用；前期我们利用去甲基化建立了γδTreg的培养体系，首次发现去甲基化诱导的γδTreg具备更强的aGVHD 负向调控作用且ICOS表达上调。预实验表明，阻断ICOS表达的γδTreg不能抑制脂多糖（LPS）诱导的树突状细胞(DC)成熟，提示去甲基化诱导该细胞ICOS上调后ICOS/B7RP-1通路增强可能在诱导耐受性DC生成致负向调控ａGVHD中起关键作用。本项目拟通过体外细胞共培养明确γδTreg不同ICOS水平对耐受性DC生成(抑制DC成熟和黏附迁移)的影响及其分子机制(影响STAT3、NF-κB、MAKP和PKC活性等)，进而在小鼠aGVHD模型中验证上述作用和机制。本研究将阐明γδTreg调控ａGVHD的新机制，为发现调控aGVHD的新靶点奠定基础

Acute graft versus host disease (aGVHD) is a major complication after allogeneic hematopoietic stem cell transplantation. Regulatory γδT cells (γδTregs) is a novel subset of T cells with negative immunoregulation property. In our previous study we have established a high efficient induction,expansion and enrichment system of γδTregs. And for the first time we found that demethylation-induced γδTregs had an enhanced role in aGVHD prevention. Moreover, higher expression level of ICOS were found in demethylation-induced γδTregs than in common γδTregs. ICOS plays important roles in negative immunoregulation. So we hypothesized that enhanced ICOS expression might play important roles in tolerant dendritic cell induction thus contributed to reduced instensity of aGVHD via enhanced ICOS/B7RP-1 signaling pathway. The current study will first clarify different ICOS expression levels on γδTregs have important roles in tolerant dendritic cell induction including inhibiting DC maturation, DC attachment and migration as well as its underlying mechanisms(STAT3,NF-κB, MAKP，PKC ). Next we will verify the above roles and mechanisms in aGVHD mice model. The research can lay the foundation for novel mechanisms ofγδTregs on GVHD regulation and try to find new regulation target.And also the research will provide novel clues for GVHD prevention and treatment.