Dimethyl fumarate treatment alters NK cell function in multiple sclerosis

Abstract

Dimethyl fumarate (DMF) treatment in multiple sclerosis (MS) increased the proportion of immunoregulatory CD56 NK cells and this change was proportional to reductions in CD8 memory T cells. DMF and monomethyl fumarate (MMF) treatment in vitro had directs effects on NK cells and promoted degranulation and cytotoxicity.

Targeting immunometabolism as an anti-inflammatory strategy

“…7 Furthermore, DMF promotes cytotoxicity and degranulation of Natural Killer (NK) cells, and by altering populations of NK cells, DMF increases CD56 bright NK cell numbers, thereby limiting autoimmunity through controlling the population of autoreactive T cells. 8 In addition, analyzing subsets of peripheral immune cell subsets from MS patients undergoing DMF therapy revealed an expansion of FoxP3 + regulatory T cells, CD56bright NK cells and plasmacytoid dendritic cells accompanied by a decrease in CD8 + T cells, B cells and type 1 myeloid dendritic cells. 9 Limiting peripheral autoreactive T cell counts following treatment with DMF was a phenomenon first identified in psoriasis patients, but has also been reported in MS patients.…”

Enhancing natural killer cells is beneficial in multiple sclerosis – Commentary

“…5,[7][8][9] As underscored in the commentary by Dr Laroni, an interest in NK cells as regulators of the human disease was rekindled by mechanistic substudies of MS clinical trials that revealed an association between the therapeutic efficacy of disease-modifying therapies (DMTs), or autologous hematopoietic stem cell transplantation, and the expansion of circulating NK cells. 7,[10][11][12][13] Of particular interest is a CD56 bright subset of NK cells that were first found to accumulate in the blood of MS patients treated with daclizumab, and subsequently in patients treated with alemtuzumab or dimethyl fumarate. [10][11][12] While compelling, these studies do not definitively distinguish between whether NK cell expansion plays a causative role in MS disease suppression or represents an epiphenomenon.…”

“…7,[10][11][12][13] Of particular interest is a CD56 bright subset of NK cells that were first found to accumulate in the blood of MS patients treated with daclizumab, and subsequently in patients treated with alemtuzumab or dimethyl fumarate. [10][11][12] While compelling, these studies do not definitively distinguish between whether NK cell expansion plays a causative role in MS disease suppression or represents an epiphenomenon. In fact, CD56 high NK cell journals.sagepub.com/home/msj Visit SAGE journals online journals.sagepub.com/ home/msj counts are not predictive of MS lesion accumulation beyond a year of daclizumab treatment, and daclizumab-treated patients whose CD56 bright NK cells did not expand still enjoyed some degree of therapeutic benefit.…”

Letters to the editor: Publish fast

“…We are pleased to announce in the second editorial for 2018 that, as of this February Issue of the European Journal of Immunology (EJI), we have introduced a new article type, Letter to the Editor . Letters to the Editor are an addition to the family of Research Articles (Full‐length articles, Short Communications, Technical Comments) published by EJI.…”

“…Content‐wise, Letters to the Editor are meant to cover a wide range of topics in basic and clinical immunology in‐line with the scope of EJI as covered in my previous editorials . The two Letters published in this issue cover clinical and basic immunology, respectively, so we're off to a good start.…”