Combinatory treatment using tacrolimus and a STAT3 inhibitor regulate Treg cells and plasma cells

Int J Immunopathol Pharmacol. 2018 Jan-Dec:32:2058738418778724. doi: 10.1177/2058738418778724.

Abstract

Systemic lupus erythematosus (SLE; lupus) is a prototypical autoimmune disease characterized by circulating autoantibodies to nuclear antigens and immune complex deposition, resulting in damage to target organs. To investigate the effects of tacrolimus (TAC) on effector T cells and B cells, we examined its involvement in the development of effector T cells, germinal center (GC) B cells, and plasma cells in an in vitro system using wild-type (WT) and lupus-prone mice. The population of T helper (Th) 1, Th2, and Th17 cells interleukin (IL)-17-producing T (Th17) cells and the production of interferon-γ and interleukin-17A IL-17A were suppressed by TAC. TAC also reduced the population of regulatory T (Treg) cells; however, a combination treatment with the signal transducer and activator of transcription 3 (STAT3) inhibitor STA-21 promoted the population of Treg cells. TAC also suppressed the populations of GC B cells and plasma cells synergistically with STA-21. These findings suggest that the application of TAC with a STAT3 signal inhibitor may provide benefits in SLE treatment.

Keywords: Th17; Treg cell; germinal center B cell; plasma cell; systemic lupus erythematosus; tacrolimus.

MeSH terms

  • Animals
  • Cells, Cultured
  • Cytokines / antagonists & inhibitors
  • Disease Models, Animal
  • Drug Therapy, Combination
  • Lupus Erythematosus, Systemic / drug therapy*
  • Lupus Erythematosus, Systemic / genetics
  • Lupus Erythematosus, Systemic / immunology
  • Mice, Inbred C57BL
  • Mice, Mutant Strains
  • Plasma Cells / drug effects*
  • Plasma Cells / immunology
  • Polycyclic Compounds / administration & dosage
  • Polycyclic Compounds / therapeutic use*
  • STAT3 Transcription Factor / antagonists & inhibitors*
  • Spleen / drug effects
  • Spleen / immunology
  • T-Lymphocytes, Regulatory / drug effects*
  • T-Lymphocytes, Regulatory / immunology
  • Tacrolimus / administration & dosage
  • Tacrolimus / therapeutic use*
  • Th1 Cells / drug effects
  • Th1 Cells / immunology
  • Th17 Cells / drug effects
  • Th17 Cells / immunology

Substances

  • Cytokines
  • Polycyclic Compounds
  • STA-21
  • STAT3 Transcription Factor
  • Stat3 protein, mouse
  • Tacrolimus