National Centre for Neuroimmunology and Emerging Diseases, Menzies Health Institute, Griffith University, Gold Coast 4215, Australia.
Consortium Health International for Myalgic Encephalomyelitis, Menzies Health Institute Queensland, Griffith University, Gold Coast 4215, Australia.
Biomolecules. 2023 Jun 26;13(7):1039. doi: 10.3390/biom13071039.
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a disabling multisystemic condition. The pathomechanism of ME/CFS remains unestablished; however, impaired natural killer (NK) cell cytotoxicity is a consistent feature of this condition. Calcium (Ca) is crucial for NK cell effector functions. Growing research recognises Ca signalling dysregulation in ME/CFS patients and implicates transient receptor potential ion channel dysfunction. TRPM7 (melastatin) was recently considered in the pathoaetiology of ME/CFS as it participates in several Ca-dependent processes that are central to NK cell cytotoxicity which may be compromised in ME/CFS. TRPM7-dependent Ca influx was assessed in NK cells isolated from n = 9 ME/CFS patients and n = 9 age- and sex-matched healthy controls (HCs) using live cell fluorescent imaging techniques. Slope ( < 0.05) was significantly reduced in ME/CFS patients compared with HCs following TRPM7 activation. Half-time of maximal response ( < 0.05) and amplitude ( < 0.001) were significantly reduced in the HCs compared with the ME/CFS patients following TRPM7 desensitisation. Findings from this investigation suggest that TRPM7-dependent Ca influx is reduced with agonism and increased with antagonism in ME/CFS patients relative to the age- and sex-matched HCs. The outcomes reported here potentially reflect TRPM3 dysfunction identified in this condition suggesting that ME/CFS is a TRP ion channelopathy.
肌痛性脑脊髓炎/慢性疲劳综合征（ME/CFS）是一种使人丧失能力的多系统疾病。ME/CFS 的发病机制尚未确定；然而，自然杀伤（NK）细胞细胞毒性受损是这种疾病的一个一致特征。钙（Ca）对 NK 细胞效应功能至关重要。越来越多的研究认识到 ME/CFS 患者的 Ca 信号转导失调，并暗示瞬时受体电位离子通道功能障碍。TRPM7（melastatin）最近被认为是 ME/CFS 发病机制中的一个因素，因为它参与了几个对 NK 细胞细胞毒性至关重要的 Ca 依赖性过程，而这些过程在 ME/CFS 中可能受到损害。使用活细胞荧光成像技术，评估了从 n = 9 名 ME/CFS 患者和 n = 9 名年龄和性别匹配的健康对照者（HCs）中分离出的 NK 细胞中 TRPM7 依赖性 Ca 内流。TRPM7 激活后，ME/CFS 患者的斜率明显低于 HCs（<0.05）。TRPM7 脱敏后，与 ME/CFS 患者相比，HCs 的最大反应半时（<0.05）和幅度（<0.001）明显降低。与年龄和性别匹配的 HCs 相比，ME/CFS 患者的 TRPM7 依赖性 Ca 内流在激动时减少，在拮抗时增加。本研究的结果表明，与年龄和性别匹配的 HCs 相比，ME/CFS 患者的 TRPM7 依赖性 Ca 内流在激动时减少，在拮抗时增加。这里报告的结果可能反映了该疾病中发现的 TRPM3 功能障碍，表明 ME/CFS 是一种 TRP 离子通道病。
