Altered TRPM7-Dependent Calcium Influx in Natural Killer Cells of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Patients

Stanley Du Preez; Natalie Eaton-Fitch; Peter K Smith; Sonya Marshall-Gradisnik

doi:10.3390/biom13071039

Altered TRPM7-Dependent Calcium Influx in Natural Killer Cells of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Patients

Biomolecules. 2023 Jun 26;13(7):1039. doi: 10.3390/biom13071039.

Authors

Stanley Du Preez^{1

2

3

4}, Natalie Eaton-Fitch^{1

2}, Peter K Smith^{4

5}, Sonya Marshall-Gradisnik^{1

2}

Affiliations

¹ National Centre for Neuroimmunology and Emerging Diseases, Menzies Health Institute, Griffith University, Gold Coast 4215, Australia.
² Consortium Health International for Myalgic Encephalomyelitis, Menzies Health Institute Queensland, Griffith University, Gold Coast 4215, Australia.
³ School of Pharmacy and Medical Sciences, Griffith University, Gold Coast 4215, Australia.
⁴ School of Medicine and Dentistry, Griffith University, Gold Coast 4215, Australia.
⁵ Queensland Allergy Services, Gold Coast 4215, Australia.

Abstract

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 (Ca²⁺) is crucial for NK cell effector functions. Growing research recognises Ca²⁺ 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 Ca²⁺-dependent processes that are central to NK cell cytotoxicity which may be compromised in ME/CFS. TRPM7-dependent Ca²⁺ 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 (p < 0.05) was significantly reduced in ME/CFS patients compared with HCs following TRPM7 activation. Half-time of maximal response (p < 0.05) and amplitude (p < 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 Ca²⁺ 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.

Keywords: calcium; chronic fatigue syndrome; myalgic encephalomyelitis; natural killer cell; transient receptor potential melastatin 7.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Calcium / metabolism
Fatigue Syndrome, Chronic*
Humans
Killer Cells, Natural / metabolism
Protein Serine-Threonine Kinases
TRPM Cation Channels*
Transient Receptor Potential Channels*

Substances

Calcium
TRPM Cation Channels
Transient Receptor Potential Channels
TRPM7 protein, human
Protein Serine-Threonine Kinases

Grants and funding

This research was funded by the Stafford Fox Medical Research Foundation (grant number 489798), National Health and Medical Research Council (grant number 1199502), Ian and Talei Stewart, McCusker Charitable Foundation (grant number 49979), Buxton Foundation (grant number 4676), Henty Community (grant number 4879), Henty Lions Club (grant number 4880), Mason Foundation (grant number 47107), Mr Douglas Stutt, Blake Beckett Trust Foundation (grant number 4579), Alison Hunter Memorial Foundation (grant number 4570) and the Change for ME Charity (grant number 4575).