Regular physical exercise has been recognized as a potent modulator of immune function, with its effects including enhanced immune surveillance, reduced inflammation, and improved overall health. While strong evidence exists that physical exercise affects the specific expression and activity of non-coding RNAs (ncRNAs) also involved in immune system regulation, heterogeneity in individual study designs and analyzed exercise protocols exists, and a condensed list of functional, exercise-dependent ncRNAs with known targets in the immune system is missing from the literature. A systematic review and qualitative analysis was used to identify and categorize ncRNAs participating in immune modulation by physical exercise. Two combined approaches were used: (a) a systematic literature search for “ncRNA and exercise immunology”, (b) and a database search for microRNAs (miRNAs) (miRTarBase and DIANA-Tarbase v8) aligned with known target genes in the immune system based on the Reactome database, combined with a systematic literature search for “ncRNA and exercise”. Literature searches were based on PubMed, Web of Science, and SPORTDiscus; and miRNA databases were filtered for targets validated by experimental data. Studies were eligible if they reported on exercise-based interventions in healthy humans. After duplicate removal, 95 studies were included reporting on 164 miRNAs, which were used for the qualitative synthesis. Six studies reporting on long-noncoding RNAs (lncRNAs) or circular RNAs were also identified. Results were analyzed using ordering tables that included exercise modality (endurance/resistance exercise), acute or chronic interventions, as well as the consistency in reported change between studies. Evaluation criteria were defined as “validated” with 100% of ≥3 independent studies showing identical direction of regulation, “plausible” (≥80%), or “suggestive” (≥70%). For resistance exercise, upregulation of miR-206 was validated while downregulation of miR-133a appeared plausible. For endurance exercise, 15 miRNAs were categorized as validated, with 12 miRNAs being consistently elevated and 3 miRNAs being downregulated, most of them after acute exercise training. In conclusion, our approach provides evidence that miRNAs play a major role in exercise-induced effects on the innate and adaptive immune system by targeting different pathways affecting immune cell distribution, function, and trafficking as well as production of (anti-)inflammatory cytokines. miRNAs miR-15, miR-29c, miR-30a, miR-142/3, miR-181a, and miR-338 emerged as key players in mediating the immunomodulatory effects of exercise predominantly after acute bouts of endurance exercise.

中文翻译：

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运动免疫学中的非编码 RNA：系统评价

定期体育锻炼被认为是免疫功能的有效调节剂，其作用包括增强免疫监视、减少炎症和改善整体健康。虽然有强有力的证据表明体育锻炼会影响也参与免疫系统调节的非编码 RNA (ncRNA) 的特异性表达和活性，但个体研究设计和分析的运动方案存在异质性，并且功能性、运动依赖性 ncRNA 的简明列表文献中缺少免疫系统中已知目标的研究。通过系统评价和定性分析，对参与体育锻炼免疫调节的 ncRNA 进行识别和分类。使用了两种组合方法：(a) 系统文献搜索“ncRNA 和运动免疫学”，(b) 数据库搜索与免疫系统中已知靶基因对齐的 microRNA (miRNA)（miRTarBase 和 DIANA-Tarbase v8）基于Reactome数据库，结合“ncRNA与运动”的系统文献检索。文献检索基于 PubMed、Web of Science 和 SPORTDiscus；并筛选 miRNA 数据库以寻找经实验数据验证的目标。如果研究报告了对健康人类进行基于运动的干预措施，那么这些研究就是合格的。重复去除后，纳入了 95 项研究，报告了 164 种 miRNA，用于定性合成。还确定了六项关于长非编码 RNA (lncRNA) 或环状 RNA 的研究报告。使用排序表对结果进行分析，其中包括运动方式（耐力/抗阻运动）、急性或慢性干预措施，以及研究之间报告的变化的一致性。评估标准被定义为“已验证”，≥3 项独立研究 100% 显示相同的监管方向，“合理”(≥80%) 或“建议性”(≥70%)。对于抗阻运动，miR-206 的上调得到了验证，而 miR-133a 的下调似乎是合理的。对于耐力运动，15 个 miRNA 被归类为经过验证的，其中 12 个 miRNA 持续升高，3 个 miRNA 下调，其中大多数在急性运动训练后。总之，我们的方法提供了证据，表明 miRNA 通过针对影响免疫细胞分布、功能和运输以及（抗）炎细胞因子产生的不同途径，在运动引起的先天性和适应性免疫系统影响中发挥着重要作用。 miRNA miR-15、miR-29c、miR-30a、miR-142/3、miR-181a 和 miR-338 在介导运动免疫调节作用（主要是在急性耐力运动后）发挥着关键作用。