Department of Rehabilitation Sciences, Faculty of Health, University of Witten/Herdecke, Witten 58455, Germany; DRV Clinic Königsfeld, Center for Medical Rehabilitation, Ennepetal 58256, Germany.
Department of Rehabilitation Sciences, Faculty of Health, University of Witten/Herdecke, Witten 58455, Germany; DRV Clinic Königsfeld, Center for Medical Rehabilitation, Ennepetal 58256, Germany.
J Sport Health Sci. 2024 May;13(3):311-338. doi: 10.1016/j.jshs.2023.11.001. Epub 2023 Nov 3.
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 in vitro 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.
定期进行身体锻炼已被公认为是一种有效的免疫功能调节剂，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身体锻炼会影响非编码 RNA（ncRNA）的特定表达和活性，这些 ncRNA 也参与免疫系统的调节，但个体研究设计和分析的运动方案存在异质性，并且文献中缺少一份已知在免疫系统中有功能且与运动相关的 ncRNA 的简明清单。本系统评价和定性分析旨在确定并分类通过身体锻炼参与免疫调节的 ncRNA。采用了两种联合方法：（a）系统地搜索文献中的“ncRNA 和运动免疫学”，（b）基于 Reactome 数据库，对与免疫系统中的已知靶基因相匹配的 microRNAs（miRNAs）（miRTarBase 和 DIANA-Tarbase v8）进行数据库搜索，并结合“ncRNA 和运动”的系统文献搜索。文献检索基于 PubMed、Web of Science 和 SPORTDiscus；miRNA 数据库经过筛选，纳入了经过体外实验数据验证的靶标。如果研究报告了健康人群中基于运动的干预措施，则符合入选标准。在去除重复项后，共纳入了 95 项研究，这些研究报告了 164 个 miRNAs，用于定性综合分析。还确定了 6 项报告长链非编码 RNA（lncRNA）或环状 RNA 的研究。使用包含运动方式（耐力/抗阻运动）、急性或慢性干预以及研究间报告的变化一致性的排序表来分析结果。评估标准定义为“验证”，即≥3 项独立研究均显示出相同的调节方向，“合理”（≥80%）或“提示”（≥70%）。对于抗阻运动，miR-206 的上调得到验证，而 miR-133a 的下调似乎合理。对于耐力运动，有 15 个 miRNAs 被归类为验证，其中 12 个 miRNAs 持续升高，3 个 miRNAs 下降，其中大多数在急性运动训练后出现。总之，我们的方法提供了证据表明，miRNAs 通过靶向影响免疫细胞分布、功能和迁移以及（抗炎）细胞因子产生的不同途径，在运动诱导的先天和适应性免疫系统效应中发挥主要作用。miRNAs miR-15、miR-29c、miR-30a、miR-142/3、miR-181a 和 miR-338 作为主要参与者，在介导运动的免疫调节作用方面发挥作用，主要发生在急性耐力运动后。
