FOXP3+调节性T细胞（FOXP3+Treg）抑制功能降低，导致其与效应细胞失衡是银屑病免疫紊乱的重要环节。链球菌等感染促进银屑病中防御素hBD2分泌。我们发现，有别于对效应细胞的促炎，hBD2促进银屑病FOXP3+Treg分泌IL-10，但机制不清（不影响FOXP3）。TLR2/4信号通路参与银屑病发展，且预实验证实TLR2/4拮抗可降低Treg的关键功能因子PRDM1，并伴随hBD2上调IL-10作用的减弱。故结合研究基础，我们提出hBD2通过TLR2/4-PRDM1轴协同FOXP3增强Treg抑制功能。拟在T细胞、细胞系和动物模型水平，观察分析不同浓度hBD2对银屑病FOXP3+Treg抑制功能的影响，明确TLR2/4-PRDM1轴在其中的作用和具体调控的分子机制，为纠正银屑病FOXP3+Treg功能紊乱提供干预新靶点，为研究FOXP3+Treg在自身免疫病中的调控机制奠定基础。

The downregulation of FOXP3+ regulatory T cells (FOXP3+Treg) and its imbalance with effector cells have been identified as the key factors in the pathogenesis of psoriasis by ours and other research groups. Streptococcus infection can increase the secretion of human β-defensin 2 (hBD2) in psoriasis. In our preliminary experiment, we found that hBD2 could enhance Treg to secret IL-10, without effecting the transcription factor of FOXP3. The mechanism behind it is unknown. This is a striking contrast to its proinflammatory function in effector cells. TLR2/4 pathway has been demonstrated to be associated with psoriasis develoment. Our preliminary study showed that antagonism of TLR2/4 pathway decreased the key factor of PRDM1(Positive regulatory domain I) level in Treg and the upregulation of IL-10 by hBD2 was also decreased. Based on these, we propose that hBD2 enhance FOXP3+Treg by TLR2/4-PRDM1 axis. We plan to analyze the effects of hBD-2 on psoriatic FOXP3+Treg and to identify the molecular mechanism on the levels of psoriatic immune cells, cell lines and animal modes. Our study will help to find new target for enhancing Treg function in psoriais and to establish the regulatory mechanism of FOXP3+Treg in autoimmune disorders.

FOXP3+调节性T细胞（FOXP3+Treg）抑制功能降低，导致其与效应细胞失衡是银屑病免疫紊乱的重要环节。链球菌等感染促进银屑病中防御素hBD2分泌。我们发现，有别于对效应细胞的促炎，hBD2促进银屑病FOXP3+Treg分泌IL-10，但机制不清（不影响FOXP3）。TLR2/4信号通路参与银屑病发展，且预实验证实TLR2/4拮抗可降低Treg的关键功能因子PRDM1，并伴随hBD2上调IL-10作用的减弱。故结合研究基础，我们提出hBD2通过TLR2/4—PRDM1轴协同FOXP3增强Treg抑制功能。拟在T细胞、细胞系和动物模型水平，观察分析不同浓度hBD2对银屑病FOXP3+Treg抑制功能的影响，明确TLR2/4—PRDM1轴在其中的作用和具体调控的分子机制，为纠正银屑病FOXP3+Treg功能紊乱提供干预新靶点，为研究FOXP3+Treg在自身免疫病中的调控机制奠定基础。