β-glucan triggers spondylarthritis and Crohn's disease-like ileitis in SKG mice
β-glucan triggers spondylarthritis and Crohn's disease-like ileitis in SKG mice
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DOI：
10.1002/art.34423
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发表时间：
2012-07-01
影响因子：
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通讯作者：
Thomas, Ranjeny
中科院分区：
文献类型：
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作者：
Ruutu, Merja;Thomas, Gethin;Thomas, Ranjeny
目的强直性脊柱炎（SpA），包括强直性脊柱炎（AS）、银屑病关节炎（PsA）、反应性关节炎和炎症性肠病相关关节炎，可引起大周围和轴关节、眼睛、皮肤、回肠和结肠的慢性炎症。遗传学研究揭示了AS、PsA和克罗恩病的共同候选基因，包括IL23R、IL12B、STAT3和CARD9，它们都与dectin 1 β -葡聚糖受体下游的白介素-23 （IL-23）信号传导有关。在ZAP-70突变的自身免疫易感SKG小鼠中，il -17依赖性炎症性关节炎在dectin 1介导的真菌感染后发生，该突变可减弱T细胞受体信号并增加T细胞的自身反应性。本研究旨在确定注射1,3- β -葡聚糖（curdlan）的SKG小鼠是否会出现SpA的证据，以及先天和适应性自身免疫与这一过程的关系。方法分别给SKG小鼠和对照组BALB/c小鼠注射一次凝乳素或甘露聚糖。每周对关节炎进行评分，并评估器官的病理特征。将抗il -23单克隆抗体注射到经curdlan处理的SKG小鼠体内。将curdlan处理小鼠的CD4+ T细胞转移到SCID小鼠，分析血清中的自身抗体。结果全身注射curdlan后，SKG小鼠出现鼻炎、手腕、踝关节和骶髂关节关节炎、趾炎、足底筋膜炎、椎体炎症、类似克罗恩病的回肠炎和单侧葡萄膜炎。甘露南引发了脊柱炎和关节炎。关节炎和脊柱炎依赖于T细胞和il -23，并可转移给CD4+ T细胞的SCID受体。SpA与胶原蛋白和蛋白聚糖特异性自身抗体相关。我们的研究结果表明，SKG ZAP-70W163C突变使BALB/c小鼠在全身性暴露于β -葡聚糖或甘露聚糖后，由于先天和适应性自身免疫而易患SpA。
Objective The spondylarthritides (SpA), including ankylosing spondylitis (AS), psoriatic arthritis (PsA), reactive arthritis, and arthritis associated with inflammatory bowel disease, cause chronic inflammation of the large peripheral and axial joints, eyes, skin, ileum, and colon. Genetic studies reveal common candidate genes for AS, PsA, and Crohn's disease, including IL23R, IL12B, STAT3, and CARD9, all of which are associated with interleukin-23 (IL-23) signaling downstream of the dectin 1 beta-glucan receptor. In autoimmune-prone SKG mice with mutated ZAP-70, which attenuates T cell receptor signaling and increases the autoreactivity of T cells in the peripheral repertoire, IL-17dependent inflammatory arthritis developed after dectin 1mediated fungal infection. This study was undertaken to determine whether SKG mice injected with 1,3-beta-glucan (curdlan) develop evidence of SpA, and the relationship of innate and adaptive autoimmunity to this process. Methods SKG mice and control BALB/c mice were injected once with curdlan or mannan. Arthritis was scored weekly, and organs were assessed for pathologic features. AntiIL-23 monoclonal antibodies were injected into curdlan-treated SKG mice. CD4+ T cells were transferred from curdlan-treated mice to SCID mice, and sera were analyzed for autoantibodies. Results After systemic injection of curdlan, SKG mice developed enthesitis, wrist, ankle, and sacroiliac joint arthritis, dactylitis, plantar fasciitis, vertebral inflammation, ileitis resembling Crohn's disease, and unilateral uveitis. Mannan triggered spondylitis and arthritis. Arthritis and spondylitis were T cell and IL-23dependent and were transferable to SCID recipients with CD4+ T cells. SpA was associated with collagen- and proteoglycan-specific autoantibodies. Conclusion Our findings indicate that the SKG ZAP-70W163C mutation predisposes BALB/c mice to SpA, resulting from innate and adaptive autoimmunity, after systemic beta-glucan or mannan exposure.