Physiological strength electric fields modulate human T cell activation and polarisation

Abstract

The factors and signals driving T cell activation and polarisation during immune responses have been studied mainly at the level of cells and chemical mediators. Here we describe a physical driver of these processes in the form of physiological-strength electric fields (EFs). EFs are generated at sites where epithelium is disrupted (e.g. wounded skin/bronchial epithelia) and where T cells frequently are present. Using live-cell imaging, we show human primary T cells migrate directionally to the cathode in low strength (50/150 mV/mm) EFs. Strikingly, we show for the first time that EFs significantly downregulate T cell activation following stimulation with antigen-activated APCs or anti-CD3/CD28 antibodies, as demonstrated by decreased IL-2 secretion and proliferation. These EF-induced functional changes were accompanied by a significant dampening of CD4+ T cell polarisation. Expression of critical markers of the Th17 lineage, RORγt and IL-17, and the Th17 polarisation mediator phospho-STAT3 were reduced significantly, while STAT1, ERK and c-Jun phosphorylation were comparatively unaffected suggesting STAT3 modulation by EFs as one mechanism driving effects. Overall, we identify electrical signals as important contributors to the co-ordination and regulation of human T cell functions, paving the way for a new research area into effects of naturally occurring and clinically-applied EFs in conditions where control of T cell activity is paramount.

Hydrogels for Engineering the Immune System

“…For example, literature using hydrogels to regenerate the lymphatic system are primarily focused on controlled release of growth factors and encapsulation of cell for transplantation. Such system could also benefit from the use of remotely actuatable hydrogels to apply biomechanical [ 136 ] or bioelectrical signals [ 137 ] to promote tissue regeneration or bias immune cell differentiation. By expanding the synthesis methods of immune‐modulatory hydrogels, the material can also be used as coatings to prevent and minimize implant‐related microbial infection, in addition to their current use as injectable materials.…”

Cardio‐microcurrent device for chronic heart failure: first‐in‐human clinical study

“…Endogenous electrical microcurrent is responsible for a large number of effects. It can modulate inflammation by down‐regulating pro‐inflammatory cytokines and regulating macrophage function and T‐cell activation 30–33 …”

Cytotoxic T cells response with decreased CD4/CD8 ratio during mammary tumors inhibition in rats induced by non-contact electric fields

“…Instead, it helped wound healing after cancer treatment in rats of IT group, indicated by the drying wound and the reduction of wound size (Figure 3b and Figure 3c). Endogenous electric fields are known to play as a signal that direct cell migration in epithelial wound healing and external electric fields exposure may accelerate wound healing by directing the migration of T cells 19 and fibroblast, as well as their proliferation and transdifferentiation 41,42 . In addition, Hoare et al 20 reported that external electric fields may contribute to the coordination and regulation of macrophage functions, including wound healing.…”

“…Petri et al 18 reported that static electric fields increase the immune response in mice. Moreover, electric fields modulate the activation and polarisation of some immune cells, including T cells 19 and macrophages 20 . Voloshin et al 21 reported that TTFields exposure combined with anti-PD-1 therapy induced immunogenic cell death in lung and colon tumors.…”