Expression of FcgammaRIII is required for development of collagen-induced arthritis.
Expression of FcgammaRIII is required for development of collagen-induced arthritis.
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FcgammaRIII 的表达是胶原诱导性关节炎发展所必需的。
DOI：
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发表时间：
2002
影响因子：
5.4
通讯作者：
S. Kleinau
中科院分区：
文献类型：
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作者：
T. Díaz de Ståhl;M. Andrén;Pernilla Martinsson;J. Verbeek;S. Kleinau
循环免疫复合物与风湿性免疫疾病的发病机制有关，这些免疫复合物与 IgG Fc 受体 (FcgammaR) 的相互作用似乎是炎症过程启动的决定性步骤。先前已证明，缺乏 FcRgamma 链并因此缺乏多个 FcR 的小鼠可以免受胶原诱导的关节炎 (CIA) 的影响。然而，不同 FcgammaR 的相对贡献尚未确定。在本研究中，我们研究了 FcgammaRIII（激活低亲和力 FcgammaR）在 CIA 发展中的表达和贡献。用弗氏完全佐剂中的牛II型胶原蛋白(BCII)对野生型和FcgammaRIII缺陷型DBA/1 (FcgammaRIII(-/-))小鼠进行免疫，并通过临床和组织学检查评估关节炎的发展。我们发现，与野生型小鼠相比，FcgammaRIII(-/-) 小鼠几乎没有出现关节炎，其中大多数小鼠出现了严重的 CIA。尽管对 CIA 有抵抗力，但 FcgammaRIII(-/-) 小鼠对 BCII 的体液和细胞反应与野生型对照小鼠相似。在使用 FcgammaRII 和 FcgammaRIII 特异性的 mAb 2.4G2 染色的 FcgammaRII 缺陷 DBA/1 小鼠正常关节切片上研究了 FcgammaRIII 表达。 FcgammaRIII 在滑膜内层和下层细胞中得到证实。我们得出的结论是，CIA 的发展需要 FcgammaRIII，并且 FcgammaRIII 在滑膜细胞上的表达可能有助于抗体触发的关节炎症。
Circulating immune complexes are implicated in the pathogenesis of rheumatic immune disorders and the interaction of these immune complexes with IgG Fc receptors (FcgammaR) seems to be a determining step in the initiation of the inflammatory process. Mice deficient in the FcRgamma-chain, and thus lacking multiple FcR, have previously been shown to be protected from collagen-induced arthritis (CIA). However, the relative contribution of the different FcgammaR has not been identified. In this study, we investigated the expression and contribution of FcgammaRIII, the activating low-affinity FcgammaR in the development of CIA. Wild-type and FcgammaRIII-deficient DBA/1 (FcgammaRIII(-/-)) mice were immunized with bovine collagen type II (BCII) in Freund's complete adjuvant and arthritis development was evaluated by clinical and histological examinations. We found that FcgammaRIII(-/-) mice developed virtually no arthritis in contrast to wild-type mice, the majority of which developed severe CIA. Although resistant to CIA, the humoral and cellular responses to BCII in FcgammaRIII(-/-) mice were similar to that seen in wild-type controls. FcgammaRIII expression was studied on sections from normal joints of FcgammaRII-deficient DBA/1 mice stained with the mAb 2.4G2, specific for FcgammaRII and FcgammaRIII. FcgammaRIII was demonstrated in cells of the lining and sublining layer of the synovial membrane. We conclude that development of CIA requires FcgammaRIII and that expression of FcgammaRIII on synovial cells may contribute to the antibody-triggered inflammation in joints.