Irmler Ingo M, Gajda Mieczyslaw, Kamradt Thomas
Institute of Immunology, University Hospital Jena, Jena, Germany.
Institute of Pathology, University Hospital Jena, Jena, Germany.
Ann Rheum Dis. 2014 Dec;73(12):2183-91. doi: 10.1136/annrheumdis-2013-204148. Epub 2013 Dec 10.
Clinical evidence suggests that neurological lesions can protect from arthritis. Acute cerebral ischaemia induces severe immunosuppression, resulting in enhanced susceptibility to infections. We aimed to determine if stroke-induced immunosuppression can ameliorate arthritis and to delineate the immunological mechanisms involved.
Unilateral cerebral ischaemia was induced in mice by occlusion of one middle cerebral artery (MCAO) at different time points after induction of G6PI-induced arthritis in mice. Clinical and histological signs of arthritis were assessed. Regulatory T cells were specifically depleted by injection of diphtheria toxin into transgenic DEREG mice. Immunological correlates of MCAO were determined by flow cytometry and serological methods.
MCAO reduced the clinical and histological signs of arthritis significantly. To be effective, stroke had to be induced during the induction phase or the early clinical stage of arthritis. MCAO induced a global loss of leucocytes. Despite the reduced absolute number of lymphocytes, the functional differentiation of T helper cells into Th1/17 cells and the production of autoantibodies were unimpaired. Depletion experiments showed that regulatory T cells were dispensable for the protective effect of MCAO.
MCAO ameliorates arthritis. The correlate of protection from arthritis is not the reduction of a particular pathogenic leucocyte subset or the preferential expansion or emergence of a protective cell population but the global reduction of leucocytes during arthritis.
临床证据表明神经损伤可预防关节炎。急性脑缺血会导致严重的免疫抑制，从而增加感染易感性。我们旨在确定中风诱导的免疫抑制是否能改善关节炎，并阐明其中涉及的免疫机制。
在小鼠诱导G6PI诱导的关节炎后的不同时间点，通过闭塞一侧大脑中动脉（MCAO）诱导小鼠单侧脑缺血。评估关节炎的临床和组织学体征。通过向转基因DEREG小鼠注射白喉毒素特异性清除调节性T细胞。通过流式细胞术和血清学方法确定MCAO的免疫相关因素。
MCAO显著减轻了关节炎的临床和组织学体征。为了产生效果，中风必须在关节炎的诱导期或早期临床阶段诱发。MCAO导致白细胞整体减少。尽管淋巴细胞绝对数量减少，但辅助性T细胞向Th1/17细胞的功能分化和自身抗体的产生并未受损。清除实验表明，调节性T细胞对于MCAO的保护作用并非必需。
MCAO可改善关节炎。预防关节炎的相关因素不是特定致病白细胞亚群的减少，也不是保护性细胞群体的优先扩增或出现，而是关节炎期间白细胞的整体减少。
