T cell-specific BLIMP-1 deficiency exacerbates experimental autoimmune encephalomyelitis in nonobese diabetic mice by increasing Th1 and Th17 cells

• T cell-specific BLIMP-1 abrogation significantly aggravates EAE.
• BLIMP-1 ablation markedly increases encephalitogenic Th1 and Th17 cells in CNS.
• BLIMP-1 deficiency impairs the homeostasis and IL-10 production of Treg cells in CNS.
• BLIMP-1 cell-intrinsically modulates the phosphorylation of Stat3Y705 and Stat4Y693.
• Reintroduction of BLIMP-1 rescues exacerbated EAE in CKO mice.

Recently, we demonstrated that B lymphocyte-induced maturation protein 1 (BLIMP-1) has a role in regulating the differentiation and effector function of Th1 and Th17 cells. As these cells play critical roles in the induction and pathogenesis of experimental autoimmune encephalomyelitis (EAE), we investigated the potential role of T cell BLIMP-1 in modulating MOG35–55-induced EAE. We established T cell-specific BLIMP-1 conditional knockout (CKO) NOD mice to dissect the role of BLIMP-1 in EAE using loss-of-function model. Our results indicate that EAE severity is dramatically exacerbated in CKO mice. The numbers of CNS-infiltrating Th1, Th17, IFN-γ+IL-17A+, and IL-21+IL-17A+ CD4+ T cells are remarkably increased in brain and spinal cord of CKO mice. Moreover, the ratio of Tregs/effectors and IL-10 production of Tregs are significantly downregulated in CNS of CKO mice. We conclude that BLIMP-1 suppresses autoimmune encephalomyelitis via downregulating Th1 and Th17 cells and impairing Treg cells.