Autotaxin (ATX)具有lysoPLD活性，催化LPC水解生成LPA。LPA作为磷脂信号分子，通过与LPA受体结合参与多种生理和病理过程的调控。已有的研究表明ATX/LPA参与免疫反应的调节，但对其中的分子机制了解甚少。IFN-α和IFN-β统称为I型干扰素，是调节机体免疫的重要细胞因子。我们的前期研究发现，I型干扰素能够通过IFNAR介导的JAK-STAT通路诱导人单核细胞中ATX的表达；细菌脂多糖和非甲基化CpG DNA处理导致单核细胞和树突状细胞时产生的I型干扰素可以作为自分泌因子诱导免疫细胞中ATX的表达。因此，I型干扰素诱导ATX表达是激活ATX/LPA通路参与免疫调节的重要机制。在本项目中我们将进一步阐明I型干扰素诱导ATX表达的细胞和组织特异性及其分子机理，揭示ATX/LPA在免疫调节中的作用和作用机制，深入认识生物活性脂类代谢在炎症反应和自身免疫中的生物学功能。

Autotaxin (ATX) is a secreted glycoprotein with the lysophospholipase D (lysoPLD) activity to convert lysophosphatidylcholine (LPC) into lysophosphatidic acid (LPA), a bioactive lysophospholipid which is involved in diverse physiological and pathological processes through the interaction with its specific receptors on cellular membrane. It has been reported that ATX/LPA can regulate the immune activities，but how ATX-LPA axis is activated to regulate the immune activities remains largely unknown. Interferon-alpha (IFN-alpha) and IFN-beta, collectively known as type I IFNs, are the major effector cytokines modulating immune activity. In our previous study, it was found that the type I IFNs induced ATX expression in human monocytic cells through the IFN-alpha/beta receptor (IFNAR)-mediated JAK-STAT signaling pathway.Bacterial lipopolysaccharide and unmethylated CpG-DNA could induce ATX expression in both monocytic cells and dendritic cells (DCs), dependending on the production of type I IFNs. These results indicate that the induction of ATX by type I IFNs is the principal mechamism to active the ATX-LPA axis for immune regulation. In this study, we will clarify the cellular and tissue specificity, as well as the molecular mechanism, of the ATX induction by type I IFNs, elucidate the function and mechanisms of ATX-LPA axis in immune regulation, and further explore the biological function of bioactive lipid metabolism in inflamation and autoimmunity.