Department of Experimental Medical Science, Lund University, Sweden.
Genes Immun. 2010 Apr;11(3):239-45. doi: 10.1038/gene.2010.2. Epub 2010 Mar 4.
In this study, we sought to determine the effect of the quantitative trait locus Pia7 on arthritis severity. The regulatory locus derived from the arthritis-resistant E3 rat strain was introgressed into the arthritis-susceptibility DA strain through continuous backcrossing. Congenic rats were studied for their susceptibility to experimental arthritis using pristane and adjuvant oil. In addition, cell number and function of various leukocyte populations were analyzed either under naive or stimulated conditions. We found that the minimal congenic fragment of DA.E3-Pia7 rats overlapped with the minimal fragment in DA.PVG-Oia2 congenic rats, which has been positionally cloned to the antigen-presenting lectin-like receptor complex (APLEC) genes. DA.E3-Pia7 congenic rats were protected from both PIA and OIA, but the protection was more pronounced in OIA. In adoptive transfer experiments we observed that the Pia7 locus controlled the priming of arthritogenic T cells and not the effector phase. In addition, Pia7 congenic rats had a significant higher frequency of B cells and granulocytes as well as TNFalpha production after stimulation, indicating a higher activation state of cells of the innate immune system. In conclusion, this study shows that the APLEC locus is a major locus regulating the severity of experimentally induced arthritis in rats.
在这项研究中，我们试图确定 Pia7 数量性状基因座对关节炎严重程度的影响。该调节基因座来源于关节炎抗性 E3 大鼠品系，通过连续回交被引入关节炎敏感性 DA 大鼠品系。我们使用降植烷和佐剂油研究了同基因大鼠对实验性关节炎的易感性。此外，还在天然或刺激条件下分析了各种白细胞群体的数量和功能。我们发现，DA.E3-Pia7 大鼠的最小同基因片段与 DA.PVG-Oia2 同基因大鼠的最小片段重叠，该片段已被定位克隆到抗原呈递凝集素样受体复合物（APLEC）基因。DA.E3-Pia7 同基因大鼠对 PIA 和 OIA 均有保护作用，但对 OIA 的保护作用更为明显。在过继转移实验中，我们观察到 Pia7 基因座控制了致关节炎 T 细胞的启动，而不是效应阶段。此外，同基因大鼠在刺激后 B 细胞和粒细胞以及 TNFalpha 的产生频率显著升高，表明先天免疫系统细胞的激活状态更高。总之，这项研究表明，APLEC 基因座是调节大鼠实验性诱导关节炎严重程度的主要基因座。
