Sodium chloride inhibits the suppressive function of FOXP3+ regulatory T cells

Impact of environmental factors on alloimmunity and transplant fate

“…A similar deleterious effect of salt on Tregs was observed in a xenogeneic graft-versus-host disease (x-GVHD) model and in an adoptive transfer model of experimental colitis (13). Hernandez et al demonstrated that high sodium induced Treg IFN-γ production via SGK1, impairing Treg suppressive function (13). IFN-γ neutralization restored Treg inhibitory function.…”

“…Nonetheless, T cell SGK1 mediated the deleterious effect of HSD on Tregs by triggering phosphorylation of FoxO1/ FoxO3a, thereby sequestering these important Treg transcriptional factors in the cytoplasm (12). A similar deleterious effect of salt on Tregs was observed in a xenogeneic graft-versus-host disease (x-GVHD) model and in an adoptive transfer model of experimental colitis (13). Hernandez et al demonstrated that high sodium induced Treg IFN-γ production via SGK1, impairing Treg suppressive function (13).…”

Salt and Pregnancy Complications: A Proposal for Future Research

“…Conversely, a high salt treatment inhibits activities of regulatory T cells and anti-inflammatory cytokines IL-4 and IL-13 [22,23]. High salt treatment also decreases anti-inflammatory cytokines and increases inflammatory cytokines by mouse and human macrophages in vitro [24,25].…”

Over-salting ruins the balance of the immune menu

“…In macrophages, high sodium inhibits the mTOR and AKT signaling needed for differentiation to the regulatory/pro-wound healing M(IL-4+IL-13) functional phenotype (9). In Tregs, high salt-induced IFNγ secretion appears to be mediated by SGK1, as shRNA-mediated SGK1 knockdown markedly abrogated IFNγ production and restored Treg suppressive function (10). Whether SGK1 activation is directly responsible for IFNγ production and Treg dysregulation remains to be examined.…”

“…In mice fed a high-salt diet, the development/ activation of M(IL-4+IL-13) macrophages following chitin injection was inhibited, and skin wound healing was substantially delayed and incomplete. On the adaptive side of the immune response, Hernandez and colleagues (10) demonstrate that increased sodium abrogates the suppressive function of mouse and human CD4 + Tregs. Notably, increased sodium induced Treg production of IFNγ, which appears to underlie the abrogation of Treg function, as neutralization of IFNγ with specific antibody or with specific shRNA restored the regulatory function (10).…”