The role of anti-PD-1 in psoriatic inflamamtion via increased IL-17A producing gamma delta T cells 2879

Description Psoriasis is a prevalent, chronic inflammatory autoimmune skin disease characterized by erythematous papules and noticeable scaling. Programmed cell death 1 (PD-1) is a coinhibitory receptor that involved in maintaining peripheral immunotolerance. Therefore, we investigated the immunological mechanism of psoriatic inflammation in response to anti-PD-1, the blocking antibody of PD-1 pathway, which could exacerbate psoriasis. Imiquimod (IMQ) – induced psoriasis dermatitis like mouse model was used. We confirmed immunological phenomenon focused on γδ T cells, known as one of the major IL-17 producing cells in psoriasiform mouse model. As a result, anti-PD-1 injection significantly increased the ear thickness and the relative frequency of γδ T cells in skin draining lymph node (SDLN). Among CD27- γδ T cells which are known to produce IL-17, CD27- Vγ1- Vγ4- γδ T cells produce IL-17A robustly in anti-PD-1 group especially on anti-CD3 stimulation. Interestingly, anti-IL-17 blocking antibody showed superior therapeutic effects to anti-IL-23 blocking antibody in exacerbated psoriatic inflammation induced by anti-PD-1. These finding suggests that anti-PD-1 exacerbates psoriatic inflammation by increasing IL-17A produced by CD27- Vγ1- Vγ4- γδ T cells and the clinical significance of anti-IL-17 blocking antibody as a better therapeutic strategy.