Fingolimod increases CD39-expressing regulatory T cells in multiple sclerosis patients

Area of Science:

• Immunology
• Neuroimmunology
• Pharmacology

Background:

• Multiple sclerosis (MS) pathogenesis involves immune dysregulation.
• CD39, an ectoenzyme, degrades ATP and is a potential marker for regulatory T cells (Tregs).
• ATP degradation by CD39 exerts anti-inflammatory effects.

Purpose of the Study:

• To investigate immunoregulatory and inflammatory mechanisms in MS patients treated with fingolimod.
• To assess the impact of fingolimod on immune cell populations and CD39 expression.

Main Methods:

• Peripheral blood mononuclear cells (PBMCs) were analyzed from MS patients before and after fingolimod treatment.
• mRNA expression of specific genes (CD39, AHR, CYP1B1, IL-17, IL-22, FOXP3) was measured.
• Flow cytometry and methylation-specific qPCR were used to quantify immune cell proportions, including Tregs and CD39-expressing cells.

Main Results:

• Fingolimod increased CD39, AHR, and CYP1B1 mRNA levels while decreasing IL-17, IL-22, and FOXP3 mRNA.
• Treatment led to significant reductions in B cells, CD4+ T cells, and Treg proportions.
• Remaining CD4+ T cells showed enrichment in FOXP3+ cells and CD39-expressing Tregs.

Conclusions:

• Fingolimod treatment reduces circulating CD4+ T cells and B cells in MS patients.
• The study reveals additional immunoregulatory pathways activated by fingolimod, including enhanced Treg function.