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, by Stanley Du Preez , Natalie Eaton-Fitch, Helene Cabanas, Donald Staines and Sonya Marshall-Gradisnik in Int. J. Environ. Res. Public Health 2021, 18(22), 11879; [doi.org/10.3390/ijerph182211879] 12 Nov 2021  (This article belongs to the Special Issue Chronic Fatigue Syndrome: Medical, Nursing and Public Health Management)

Research abstract:

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.