Sex differences in EAE reveal common and distinct cellular and molecular components.
Sex differences in EAE reveal common and distinct cellular and molecular components.
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DOI：
10.1016/j.cellimm.2020.104242
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发表时间：
2021-01
影响因子：
4.3
通讯作者：
Vandenbark AA
中科院分区：
文献类型：
--
作者：
Wiedrick J;Meza-Romero R;Gerstner G;Seifert H;Chaudhary P;Headrick A;Kent G;Maestas A;Offner H;Vandenbark AA
实验性自身免疫性脑脊髓炎（EAE）通常用作评估与人类疾病多发性硬化症（MS）潜在相关的临床、组织学和免疫学过程的动物模型，其疾病诱导模式仍然很大程度上未知。解释小鼠 EAE 过程的一个重要警告是，用弗氏完全佐剂 (CFA) 中乳化的髓磷脂肽免疫产生的炎症效应，通常随后在某些菌株中额外注射百日咳毒素 (Ptx) 以诱导 EAE。当前的研究评估了用小鼠 (m)MOG-35–55/CFA/Ptx 免疫诱导 EAE 的雄性和雌性 C57BL/6 小鼠脊髓的临床、组织学、细胞（脾）和趋化因子驱动的过程；仅用盐水/CFA/Ptx 进行免疫（CFA，无 EAE）；或未经治疗（天真，无 EAE）。反应曲线分析采用严格而复杂的方法来解析和表征单独的 EAE 和佐剂与 Naive 基线反应的效果。结果表明，与雌性 CFA 和 EAE 小鼠相比，雄性 CFA 和 EAE 小鼠的免疫细胞及其相关细胞因子、趋化因子和受体有更强的促炎反应，但这种反应似乎被雄性抗炎、调节和检查点 T 细胞、B 细胞和单核细胞/巨噬细胞亚群百分比增加部分抵消。外周免疫反应中的这些性别差异可能解释了雄性与雌性 CFA 免疫小鼠的中枢神经系统 (CNS) 细胞浸润减少和趋化因子谱不同，以及雄性与雌性 EAE 小鼠组中观察到的 CNS 浸润和脱髓鞘减少，最终导致两性的临床 EAE 疾病严重程度相同。我们的研究结果表明，EAE 疾病的严重程度不仅取决于中枢神经系统浸润和脱髓鞘的程度，还取决于促炎细胞与调节细胞类型及其分泌的细胞因子和趋化因子的平衡。
Experimental autoimmune encephalomyelitis (EAE) is commonly used as an animal model for evaluating clinical, histological and immunological processes potentially relevant to the human disease multiple sclerosis (MS), for which the mode of disease induction remains largely unknown. An important caveat for interpreting EAE processes in mice is the inflammatory effect of immunization with myelin peptides emulsified in Complete Freund’s Adjuvant (CFA), often followed by additional injections of pertussis toxin (Ptx) in some strains to induce EAE. The current study evaluated clinical, histological, cellular (spleen), and chemokine-driven processes in spinal cords of male vs. female C57BL/6 mice that were immunized with mouse (m)MOG-35–55/CFA/Ptx to induce EAE; immunized with saline/CFA/Ptx only (CFA, no EAE); or were untreated (Naïve, no EAE). Analysis of response curves utilized a rigorous and sophisticated methodology to parse and characterize the effects of EAE and adjuvant alone vs. the Naive baseline responses. The results demonstrated stronger pro-inflammatory responses of immune cells and their associated cytokines, chemokines, and receptors in male vs. female CFA and EAE mice that appeared to be offset partially by increased percentages of male anti-inflammatory, regulatory and checkpoint T cell, B cell, and monocyte/macrophage subsets. These sex differences in peripheral immune responses may explain the reduced cellular infiltration and differing chemokine profiles in the Central Nervous System (CNS) of male vs. female CFA immunized mice and the reduced CNS infiltration and demyelination observed in male vs. female EAE groups of mice that ultimately resulted in the same clinical EAE disease severity in both sexes. Our findings suggest EAE disease severity is governed not only by the degree of CNS infiltration and demyelination, but also by the balance of pro-inflammatory vs. regulatory cell types and their secreted cytokines and chemokines.
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HLA-DRα1-MMOG-35-55治疗实验性自身免疫性脑脊髓炎可减少中枢神经系统炎症，增强M2巨噬细胞频率并促进神经保护作用。
影响因子：
9.3
作者：
Benedek G;Meza-Romero R;Jordan K;Keenlyside L;Offner H;Vandenbark AA
通讯作者：
Vandenbark AA
影响因子：
4.4
作者：
Juedes, AE;Hjelmstrom, P;Ruddle, NH
通讯作者：
Ruddle, NH
影响因子：
6.2
作者：
Berard, Jennifer L.;Wolak, Kevin;David, Samuel
通讯作者：
David, Samuel
影响因子：
4.4
作者：
Hofstetter, HH;Shive, CL;Forsthuber, TG
通讯作者：
Forsthuber, TG
影响因子：
3.3
作者：
Kaushansky, N.;Kaminitz, A.;Ben-Nun, A.
通讯作者：
Ben-Nun, A.