Altered balance of inhibitory and active Fc gamma receptors in murine autoimmune glomerulonephritis
Altered balance of inhibitory and active Fc gamma receptors in murine autoimmune glomerulonephritis
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DOI：
10.1038/ki.2008.182
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发表时间：
2008-08-01
影响因子：
19.6
通讯作者：
Kon, Yasuhiro
中科院分区：
文献类型：
--
作者：
Ichii, Osamu;Konno, Akihiro;Kon, Yasuhiro
Mag 是 MRL 衍生的肾小球肾炎易感基因座，包括分别编码抑制性 Fc γ 受体 IIB (Fc γ RIIB) 和活性 Fc γ RIII 的 Fcgr2b 和 Fcgr3 基因。我们测量了含有 MRL 1 号染色体 82-86、92-100 和 100 cM 区域的三种 B6.MRLc1 同类小鼠品系的基因平衡变化。我们发现，只有具有 92-100（包括 Fcgr 位点）的品系才会出现肾小球肾炎。与亲本品系 C57BL/6(B6) 相比，这些同类小鼠具有脾肿大、血尿素氮升高、抗 dsDNA 抗体和更高的尿白蛋白排泄。在发生肾小球肾炎之前，在 B6 的脾脏中发现了大的 CD3-（T 细胞）和 B220-（B 细胞）阳性区域。 MRLc1(92-100) 小鼠。两种 Fc 受体均在系膜细胞和树突状细胞中发现。免疫复合物清除和抗原呈递的重要位点。 Fc gamma RIII 阳性区域在同系品系中更为突出。 B6 中 Fcgr2b mRNA 较低。 MRLc1(92-100)肾脏和脾脏比B6小鼠的这些器官高，而同源品系肾脏、脾脏和胸腺中的Fcgr3表达和Fcgr3与Fcgr2b mRNA比率比肾小球肾炎之前和早期阶段的B6小鼠更高。我们得出结论，抑制性和活性 Fc γ 受体的失衡影响肾小球肾炎的发病机制。
Mag is an MRL-derived glomerulonephritis susceptibility locus that includes the Fcgr2b and Fcgr3 genes encoding the inhibitory Fc gamma receptor IIB (Fc gamma RIIB) and active Fc gamma RIII, respectively. We measured changes in gene balance in three B6.MRLc1 congenic mouse strains containing the 82-86, 92-100 and 100 cM regions of the MRL chromosome 1. We found that only the strain that has 92-100 (which includes Fcgr loci) developed glomerulonephritis. These congenic mice had splenomegaly, elevated blood urea nitrogen, anti-dsDNA antibodies and higher urinary albumin excretion compared to the parental strain C57BL/6(B6). Prior to the development of glomerulonephritis, large CD3- (T cell) and B220- (B cell) positive areas were identified in the spleens of B6. MRLc1(92-100) mice. Both Fc receptors were found in mesangial and dendritic cells; important sites of immune-complex clearance and antigen presentation. The Fc gamma RIII-positive areas were more prominent in the congenic strain. Fcgr2b mRNA was lower in the B6. MRLc1(92-100) kidney and spleen than in those organs of the B6 mice while Fcgr3 expression and the Fcgr3 to Fcgr2b mRNA ratio was higher in the congenic strain kidneys, spleen and thymus than in those of the B6 prior to and at an early stage of glomerulonephritis. We conclude that the imbalance of inhibitory and active Fc gamma receptors influences the pathogenesis of glomerulonephritis.