Characterization of IL-2 Stimulation and TRPM7 Pharmacomodulation in NK Cell Cytotoxicity and Channel Co-Localization with PIP2 in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Patients

• Published in: International journal of environmental research and public health Vol. 18; no. 22; p. 11879
• Main Authors: Du Preez, Stanley, Eaton-Fitch, Natalie, Cabanas, Helene, Staines, Donald, Marshall-Gradisnik, Sonya
• Format: Journal Article
• Language: English
• Published: Basel MDPI AG 12.11.2021; MDPI
• Subjects: Actin; Calcium ions; Calcium signalling; Chronic fatigue syndrome; Chronic illnesses; Confocal microscopy; Crosstalk; Cytotoxicity; Encephalomyelitis; Etiology; Fatigue; Flow cytometry; Interleukin 2; Intracellular signalling; Kinases; Localization; Natural killer cells; Pain; Pharmacology; Phosphatidylinositol 4,5-diphosphate; Proteins; Sleep; Stimulation; Transient receptor potential proteins
• ISSN: 1660-4601; 1661-7827; 1660-4601
• DOI: 10.3390/ijerph182211879

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex multisystemic disorder responsible for significant disability. Although a unifying etiology for ME/CFS is uncertain, impaired natural killer (NK) cell cytotoxicity represents a consistent and measurable feature of this disorder. Research utilizing patient-derived NK cells has implicated dysregulated calcium (Ca2+) signaling, dysfunction of the phosphatidylinositol-4,5-bisphosphate (PIP2)-dependent cation channel, transient receptor potential melastatin (TRPM) 3, as well as altered surface expression patterns of TRPM3 and TRPM2 in the pathophysiology of ME/CFS. TRPM7 is a related channel that is modulated by PIP2 and participates in Ca2+ signaling. Though TRPM7 is expressed on NK cells, the role of TRPM7 with IL-2 and intracellular signaling mechanisms in the NK cells of ME/CFS patients is unknown. This study examined the effect of IL-2 stimulation and TRPM7 pharmacomodulation on NK cell cytotoxicity using flow cytometric assays as well as co-localization of TRPM7 with PIP2 and cortical actin using confocal microscopy in 17 ME/CFS patients and 17 age- and sex-matched healthy controls. The outcomes of this investigation are preliminary and indicate that crosstalk between IL-2 and TRMP7 exists. A larger sample size to confirm these findings and characterization of TRPM7 in ME/CFS using other experimental modalities are warranted.