Increase in Th17 and T-reg lymphocytes and decrease of IL22 correlate with the recovery phase of acute EAE in rat.
Increase in Th17 and T-reg lymphocytes and decrease of IL22 correlate with the recovery phase of acute EAE in rat.
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Th17和T-Reg淋巴细胞的增加以及IL22的降低与大鼠急性EAE的恢复阶段相关。
DOI：
10.1371/journal.pone.0027473
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Castellano B
中科院分区：
文献类型：
--
作者：
Almolda B;Costa M;Montoya M;González B;Castellano B
实验性自身免疫性脑脊髓炎（EAE）是一种成熟的多发性硬化模型，其特征在于小胶质细胞活化和淋巴细胞浸润。在刘易斯大鼠中诱导EAE产生急性迟发性疾病，其特征为失能的单峰，随后自发和完全恢复，随后对进一步免疫产生耐受。在当前的研究中，我们已经进行了详细的动态分析，不同的淋巴细胞群和细胞因子谱沿着的诱导，峰值，恢复和恢复后阶段，在这个范例。注射MBP的大鼠被处死，专门参加他们的临床评分，并通过流式细胞术，免疫组织化学和ELISA分析了不同的T淋巴细胞群以及不同的促炎和抗炎细胞因子的动力学在脊髓中。我们的研究结果显示，在诱导期和高峰期，与免疫学的增加平行，CD 3+和CD 4+细胞的数量逐渐增加，显示出Th 1表型，但出乎意料的是，在恢复期，尽管临床体征逐渐减少，但CD 3+和CD 4+细胞的数量和比例保持不变。有趣的是，在这个恢复阶段，我们观察到Th 1细胞显著减少，Th 17和T-reg细胞显著增加。此外，我们的研究结果表明，一个特定的细胞因子表达谱沿着EAE过程的特点是IL 10和IL 17水平没有变化，IL 21的峰值下降，和高IL 22水平在诱导和峰值阶段，在恢复过程中显着下降。总之，这些结果揭示了刘易斯大鼠急性EAE模型不同阶段淋巴细胞浸润和细胞因子分泌沿着的特定模式的存在，其不同于慢性或复发缓解型小鼠模型中已经描述的模式，其中Th 17细胞主要在峰值期间发现，表明这些淋巴细胞和细胞因子在该急性EAE模型的演变中的特定作用。
Experimental autoimmune encephalomyelitis (EAE), a well-established model of multiple sclerosis, is characterised by microglial activation and lymphocyte infiltration. Induction of EAE in Lewis rats produces an acute monophasic disease characterised by a single peak of disability followed by a spontaneous and complete recovery and a subsequent tolerance to further immunizations. In the current study we have performed a detailed analysis of the dynamics of different lymphocyte populations and cytokine profile along the induction, peak, recovery and post-recovery phases in this paradigm. MBP-injected rats were sacrificed attending exclusively to their clinical score, and the different populations of T-lymphocytes as well as the dynamics of different pro- and anti-inflammatory cytokines were analysed in the spinal cord by flow cytometry, immunohistochemistry and ELISA. Our results revealed that, during the induction and peak phases, in parallel to an increase in symptomatology, the number of CD3+ and CD4+ cells increased progressively, showing a Th1 phenotype, but unexpectedly during recovery, although clinical signs progressively decreased, the number and proportion of CD3+ and CD4+ populations remained unaltered. Interestingly, during this recovery phase, we observed a marked decrease of Th1 and an important increase in Th17 and T-reg cells. Moreover, our results indicate a specific cytokine expression profile along the EAE course characterized by no changes of IL10 and IL17 levels, decrease of IL21 on the peak, and high IL22 levels during the induction and peak phases that markedly decrease during recovery. In summary, these results revealed the existence of a specific pattern of lymphocyte infiltration and cytokine secretion along the different phases of the acute EAE model in Lewis rat that differs from those already described in chronic or relapsing-remitting mouse models, where Th17-cells were found mostly during the peak, suggesting a specific role of these lymphocytes and cytokines in the evolution of this acute EAE model.
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影响因子：
6.5
作者：
Brandt, K;Bulfone-Paus, S;Rückert, R
通讯作者：
Rückert, R
影响因子：
3.3
作者：
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作者：
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Kuchroo, Vijay K.
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作者：
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通讯作者：
Castellano, Bernardo
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作者：
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