Negative regulation of dendritic cell activation in psoriasis mediated via CD100-plexin-B2.

Psoriasis is a chronic inflammatory skin disease in which dendritic cells (DCs) play a pivotal role by inducing Th1/Th17 immune responses; however, the regulation of DC activation in psoriasis remains largely unknown. Previously we found that the level of soluble CD100 was increased in sera of psoriasis patients, and CD100 promoted the activation of inflammasome in keratinocytes. In the present study, CD100 knockout mice were utilized for generation of imiquimod (IMQ)-induced psoriatic dermatitis, with the result that skin inflammation in the early, but not late, phase of the psoriatic dermatitis was significantly exacerbated compared to that in wild-type controls. This was attributed mainly to the deficiency of CD100 in hematopoietic cells. Bone marrow-derived DCs, but not T cells or keratinocytes, from CD100 knockout mice produced significantly increased levels of IL-1β, IL-36, and IL-23 upon stimulation with IMQ in a plexin-B2-dependent manner. Moreover, the surface level of plexin-B2 on DCs of psoriasis patients was lower than that of healthy individuals, and CD100 attenuated IMQ-induced production of IL-1β and IL-36 from monocyte-derived DCs of psoriasis patients. Our results uncovered a negative regulatory mechanism for DCs activation in psoriasis, which was mediated via CD100-plexin-B2 in a cell type- and receptor-specific manner.