Forsman Huamei, Islander Ulrika, Andréasson Emil, Andersson Annica, Onnheim Karin, Karlström Alexandra, Sävman Karin, Magnusson Mattias, Brown Kelly L, Karlsson Anna
University of Gothenburg, Gothenburg, Sweden.
Arthritis Rheum. 2011 Feb;63(2):445-54. doi: 10.1002/art.30118.
Galectin 3, an endogenous β-galactoside-binding lectin, plays an important role in the modulation of immune responses. The finding that galectin 3 is present in the inflamed synovium in patients with rheumatoid arthritis suggests that the protein is associated with the pathogenesis of this disease. We undertook this study to investigate the influence of galectin 3 deficiency in a murine model of arthritis.
Wild-type (WT) and galectin 3-deficient (galectin 3(-/-) ) mice were subjected to antigen-induced arthritis (AIA) through immunization with methylated bovine serum albumin. The concentration of serum cytokines (interleukin-6 [IL-6] and tumor necrosis factor α [TNFα]) and antigen-specific antibodies was evaluated using a cytometric bead array platform and enzyme-linked immunosorbent assay (ELISA). Cellular IL-17 responses were examined by flow cytometry, ELISA, and enzyme-linked immunospot assay.
The joint inflammation and bone erosion of AIA were markedly suppressed in galectin 3(-/-) mice as compared with WT mice. The reduced arthritis in galectin 3(-/-) mice was accompanied by decreased levels of antigen-specific IgG and proinflammatory cytokines. The frequency of IL-17-producing cells in the spleen was reduced in galectin 3(-/-) mice as compared with WT mice. Exogenously added recombinant galectin 3 could partially restore the reduced arthritis and cytokines in galectin 3(-/-) mice.
Our findings show that galectin 3 plays a pathogenic role in the development and progression of AIA and that the disease severity is accompanied by alterations of antigen-specific IgG levels, systemic levels of TNFα and IL-6, and frequency of IL-17-producing T cells. To our knowledge, this is the first report of in vivo evidence that galectin 3 plays a crucial role in the development of arthritis.
半乳糖凝集素3是一种内源性β-半乳糖苷结合凝集素，在免疫反应调节中起重要作用。类风湿性关节炎患者炎症滑膜中存在半乳糖凝集素3这一发现表明，该蛋白与这种疾病的发病机制有关。我们进行这项研究以调查半乳糖凝集素3缺陷在小鼠关节炎模型中的影响。
野生型（WT）和半乳糖凝集素3缺陷型（半乳糖凝集素3(-/-)）小鼠通过用甲基化牛血清白蛋白免疫诱导抗原性关节炎（AIA）。使用细胞计数珠阵列平台和酶联免疫吸附测定（ELISA）评估血清细胞因子（白细胞介素6 [IL-6]和肿瘤坏死因子α [TNFα]）和抗原特异性抗体的浓度。通过流式细胞术、ELISA和酶联免疫斑点测定检查细胞IL-17反应。
与WT小鼠相比，半乳糖凝集素3(-/-)小鼠的AIA关节炎症和骨质侵蚀明显受到抑制。半乳糖凝集素3(-/-)小鼠中关节炎减轻伴随着抗原特异性IgG和促炎细胞因子水平降低。与WT小鼠相比，半乳糖凝集素3(-/-)小鼠脾脏中产生IL-17的细胞频率降低。外源性添加的重组半乳糖凝集素3可部分恢复半乳糖凝集素3(-/-)小鼠中减轻的关节炎和细胞因子。
我们的研究结果表明，半乳糖凝集素3在AIA的发生和发展中起致病作用，并且疾病严重程度伴随着抗原特异性IgG水平、TNFα和IL-6的全身水平以及产生IL-17的T细胞频率的改变。据我们所知，这是体内证据表明半乳糖凝集素3在关节炎发展中起关键作用的首次报告。
