Inhibition of Interferon Regulatory Factor 4 Suppresses Th1 and Th17 Cell Differentiation and Ameliorates Experimental Autoimmune Encephalomyelitis

Multiple sclerosis ( MS ) is an autoimmune disease that is characterized by recurrent episodes of T‐cell‐mediated immune attack on central nervous system ( CNS ) myelin, leading to axon damage and progressive disability. Interferon regulatory factor 4 ( IRF 4) is expressed predominantly in the immune system and plays an important role in its development and function. Recent study demonstrated that IRF 4 was critical for the generation of IL ‐17‐producing Th17 cells. However, the effect of IRF 4 on experimental autoimmune encephalomyelitis ( EAE ), an animal model of MS , needs to be further investigated. In our current study, inhibition of IRF 4 with IRF 4 si RNA (Si IRF 4) decreases EAE scores and infiltration of Th1 and Th17 cells, but increases Treg infiltration. Si IRF 4 inhibits Th1 and Th17 cell differentiation in vivo and in vitro . In our DC ‐T‐cell coculture system, Si IRF 4‐treated DC s resulted in significantly less IFN ‐ γ and IL ‐17 production from T cells. Next, we adoptively transfer CD 11c + DC s from Si IRF 4‐treated mice into recipient mice and found that these CD 11c + DC s ameliorated EAE . Furthermore, CD 11c + DC s from Si IRF 4‐treated naive mice exhibited significantly reduced expression of pro‐inflammatory cytokines TNF ‐ α , IL ‐1 β , IL ‐6 and IL ‐12/ IL ‐23 (p40), and a corresponding increase in anti‐inflammatory IL ‐10 expression. In conclusion, inhibition of IRF 4 suppresses Th1 and Th17 cell differentiation and ameliorates EAE , via a direct regulation of DC s.