Glucocorticoid treatment restores the impaired suppressive function of regulatory T cells in patients with relapsing–remitting multiple sclerosis

Abstract

SummaryPatients relapsing from multiple sclerosis (MS) are treated with high-dose, short-term intravenous injection of glucocorticoid (GC), although its mechanism of action remains only partly understood. We evaluated the ex vivo and in vitro effects of GC on regulatory T cell (Treg) function in 14 relapsingremitting MS (RR-MS) patients in acute phase and 20 healthy controls (HC). Treg function was enhanced significantly after 5 days of GC treatment. Furthermore, there was a trend towards increasing proportions of CD4 + CD25 + forkhead box P3 + T cells and interleukin-10 secretion with GC treatment when compared with HC. In conclusion, GC treatment restores the impaired Treg function in patients with RR-MS in its acute phase.

Potent and multiple regulatory actions of microglial glucocorticoid receptors during CNS inflammation

“…In GR LysMCre cultures, dexamethasone does not inhibit Kv1.3 upregulation indicating that the inhibition is GR mediated. **Pr0.02, *Pr0.05 NT versus LPS treatment of GC-GR has been reported in oligodendrocytes, 43 it is also likely that these cells are susceptible to RU486 pre-treatment and are lost in greater numbers in mutants.…”

Impact of immunosuppressive drugs on the therapeutic efficacy of ex vivo expanded human regulatory T cells

“…46 Altogether, steroids may have a beneficial effect on Tregs by influencing other cells and altering the inflammatory environment. This idea was suggested by some studies reporting that glucocorticoids negatively control both Th1-and Th17-polarization in mice and humans.…”

After Moving of Regulatory T-Cell Therapy to the Clinic: Will We Need a New Tregs Source?

“…58 Many researchers described the positive effects of dexamethasone and prednisolone on expansion of Tregs by the IL-2-dependent expansion of FOXP3+CD4+CD25+ T cells 61 or maturation of Tregs by increasing FOXP3 expression, 62 and restore the impaired suppressive function of Tregs. 63 The suggesting strategies to create a tolerogenic environment to ensure the in vivo survival of the injected Tregs or enhance their longevity in vivo by tailoring this clinical immunosuppressive therapy protocol; one month prior to Treg infusion, in parallel with low-dose tacrolimus, the patients are given rapamycin, to promote selective Treg expansion in vivo, 64 beside Treg-supportive immunosuppressive regimen including anti-thymocyte globulin (ATG), to induce lymphopenia with a preferential preservation of Tregs. 65 Additionally, to limit memory T cell expansion post-ATG induction, patients are started on tacrolimus and prednisolone.…”