微环境在细胞因子IL-27治疗哮喘中的作用及机制研究

气道过敏性微环境是哮喘慢性炎症持续存在原因之一。细胞因子IL-27是新近发现的具有调节免疫和炎症的多效性因子。我们的前期研究发现哮喘患者对IL-27介导的T淋巴细胞Th2分化抑制产生耐受，不同的培养微环境对IL-27介导的抑制效应耐受，该抑制效应可因SOCS3基因下调而部分恢复。本研究为进一步探索哮喘中IL-27抑制效应失灵原因，进一步细分，检测不同微环境下包括不同免疫细胞和细胞因子组合对IL-27作用的影响。并以SOCS3基因为切入点，利用SOCS3敲除鼠，杂合鼠及野生型鼠在不同的Th2诱导条件下细胞内信号传递子的活化状态，包括STAT1/3/4与STAT6的精细平衡，探索SOCS3与IL-27在影响Th2分化中的相互作用和对话。观察SOCS3-/-免疫细胞过继输入对哮喘小鼠气道微环境的影响及它辅助IL-27减轻气道炎症的效应。为阐释哮喘细胞因子治疗异质性及寻求解决途提供崭新视角。

Airway allergic microenviroment might contribute to the maintainence of asthma chronic airway inflammation. IL-27 is a kind of newly found modulator for immune and inflammation system.Our previous data showed the resistance to IL-27 mediated Th2 inhibition in asthmatics.We also found the resistance to IL-27 mediated Th2 inhibiton when priming CD4+ T cells under different conditions.Downregulation of SOCS3 could partially restore IL-27 mediated inhibition.We plan to further explore why IL-27 lost its effect in asthma and how micro milieu(including different combination of immune cells and cytokines) affect on IL-27.In order to interpret the interaction and crosstalk between IL-27 and SOCS3 during the process of Th2 priming,CD4+T cells from wild type, SOCS3-/+,SOCS3-/- mice are going to be purified and then measure the status and quantity of intracellualr signal molecues under varied Th2-inducing conditions,for example the balance between STAT1/3/4 and STAT6.Observe the changes of airway micro milieu after adoptive transfering SOCS3-/- immune cells and the airway inflammation by treatment of IL-27 plus SOCS3-/- immune cells.This probably help us understand the heterogenecity of cytokine treatment in asthma and help to find a new way to conquer it.