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

• Published in: International journal of immunopathology and pharmacology 2018-01, Vol.32, p.2058738418778724-2058738418778724
• Main Authors: Park, Jin-Sil, Kim, Sung-Min, Hwang, Sun-Hee, Choi, Si-Young, Kwon, Ji Ye, Kwok, Seung-Ki, Cho, Mi-La, Park, Sung-Hwan
• Format: Article
• Language: English
• Subjects: Animals; Cells, Cultured; Cytokines; Cytokines - antagonists & inhibitors; Disease Models, Animal; Drug Therapy, Combination; Letter to the Editor; Lupus; 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; Spleen - drug effects; Spleen - immunology; STAT3 Transcription Factor - antagonists & inhibitors; Systemic lupus erythematosus; 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
• ISSN: 0394-6320; 2058-7384
• DOI: 10.1177/2058738418778724

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.