β-葡聚糖可引发SKG小鼠的脊柱关节炎和克罗恩病样回肠炎。

β-glucan triggers spondylarthritis and Crohn's disease-like ileitis in SKG mice.

作者信息

Ruutu Merja, Thomas Gethin, Steck Roland, Degli-Esposti Mariapia A, Zinkernagel Martin S, Alexander Kylie, Velasco Jared, Strutton Geoffrey, Tran Ai, Benham Helen, Rehaume Linda, Wilson Robert J, Kikly Kristine, Davies Julian, Pettit Allison R, Brown Matthew A, McGuckin Michael A, Thomas Ranjeny

机构信息

University of Queensland and Princess Alexandra Hospital, Brisbane, Queensland, Australia.

出版信息

Arthritis Rheum. 2012 Jul;64(7):2211-22. doi: 10.1002/art.34423.

DOI:10.1002/art.34423

PMID:22328069

Abstract

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 β-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-17-dependent inflammatory arthritis developed after dectin 1-mediated fungal infection. This study was undertaken to determine whether SKG mice injected with 1,3-β-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. Anti-IL-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-23-dependent 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 β-glucan or mannan exposure.

摘要

目的

脊柱关节炎（SpA），包括强直性脊柱炎（AS）、银屑病关节炎（PsA）、反应性关节炎以及与炎症性肠病相关的关节炎，可导致外周大关节和中轴关节、眼睛、皮肤、回肠及结肠的慢性炎症。遗传学研究揭示了AS、PsA和克罗恩病的常见候选基因，包括IL23R、IL12B、STAT3和CARD9，所有这些基因均与小胶质细胞表面的β-葡聚糖受体下游的白细胞介素-23（IL-23）信号传导相关。在具有ZAP-70突变的自身免疫易感SKG小鼠中，该突变会减弱T细胞受体信号传导并增加外周库中T细胞的自身反应性，在小胶质细胞1介导的真菌感染后会发生IL-17依赖性炎症性关节炎。本研究旨在确定注射1,3-β-葡聚糖（凝胶多糖）的SKG小鼠是否会出现SpA迹象，以及先天性和适应性自身免疫与该过程的关系。

方法

给SKG小鼠和对照BALB/c小鼠一次性注射凝胶多糖或甘露聚糖。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凝胶多糖处理的SKG小鼠体内。将经凝胶多糖处理的小鼠的CD4 + T细胞转移到SCID小鼠体内，并分析血清中的自身抗体。

结果

全身注射凝胶多糖后，SKG小鼠出现附着点炎、腕关节、踝关节和骶髂关节炎、指（趾）炎、足底筋膜炎、椎体炎症、类似克罗恩病的回肠炎以及单侧葡萄膜炎。甘露聚糖引发脊柱炎和关节炎。关节炎和脊柱炎依赖于T细胞和IL-23，并且可以通过CD4 + T细胞转移给SCID受体。SpA与胶原蛋白和蛋白聚糖特异性自身抗体相关。