Fig. 6: Proposed effect of G6PD-d on T cell function in ASCVD.
G6PD-d has generally been shown to reduce cytokine production by T cells. The impact of this effect on atherosclerosis would be dependent on whether proatherogenic or atheroprotective T cell subsets, and their cytokine production, are affected more. a Th1 and Tfh cells are considered proatherogenic. Given a reduction in their cytokines would be atheroprotective, the CVD phenotype of G6PD-d would likely not be driven by changes in these cells. b Similar to Th1 and Tfh cells, CD8 + T cell expression of TNFɑ and IFNγ is reduced by G6PD inhibition and would be atheroprotective. G6PD activity also supports granzyme B production. Reduction in granzyme B-mediated destruction of VSMCs and VECs would be atheroprotective, but impaired killing of inflammatory T cells and APCs may represent a potential proatherogenic mechanism of G6PD-d. c The roles of Th2, Th17 and Th22 cells in atherosclerosis are unclear with both atheroprotective and proatherogenic functions reported. Like Th1 and CD8 + T cells, G6PD-d may limit cytokine production by these subsets but the impact of atherosclerosis depends on whether the proatherogenic or atheroprotective functions are relatively more impaired. d Tregs produce atheroprotective IL-10 and TGFβ. However, G6PD-d increases chronic inflammation and reduces Th1 production of IL-2. Both of these conditions may result in proatherogenic exTreg formation.
