Interleukin-23 (IL-23) is a critical cytokine for maintaining pathogenic T cells in psoriasis. As IL-23 blockade is clinically effective, IL-23 receptor (IL-23R)-expressing T cells may be a pathogenic population that drive the inflammation underlying psoriasis. Th17 cells are estimated as important IL-23R-bearing cells, but other T cell subsets remain unclear. Meanwhile, a study using a psoriatic mouse model showed that PD-1 was overexpressed by IL-17A-producing T cells. However, it remains unknown which subpopulation of pathogenic T cells co-express IL-23R and PD-1 in human psoriasis skin. Therefore, we sought to characterize PD-1 expression in T cells expanded from human psoriatic skin in relation to the expression of IL-23R and CD103. T cells from lesional skin were isolated and expanded using anti-CD3/CD28 mAb and IL-2, and they were harvested and stored at -80 °C until use. The stored skin T cells were re-stimulated with anti-CD3/CD28 mAb, in the presence of IL-23 and IL-2. The cell phenotype and cytokine profile were assessed by flow cytometry.  We found that PD-1 was expressed at a high proportion in CD8+ IL-23R+ T cells, but not in CD4+ T cells. Notably, CD8+ IL-23R+ PD-1+ cells tended to produce IL-17A at a higher frequency than CD8+ IL-23R+ PD-1- T cells. Furthermore, resident memory T cells (TRM) expressing CD8+ CD103+ IL-23R+, which are retained in resolved psoriatic skin and responsible for disease recurrence, highly expressed PD-1. These results suggest that PD-1-expressing CD8+ IL-23R+ T cells are an effector cell population driving inflammation or TRM cells exerting recurrence. Interestingly, a number of case reports showed that anti-PD-1 treatment aggravates psoriasis, suggesting that activation of these effector or resident T cells exacerbates the disease. In conclusion, CD8+ IL-23R+ PD-1+ T cells could play a crucial role in maintenance and recurrence of psoriasis.

CD8+ IL-23R+ PD-1+ T cells in psoriatic skin possibly play a role in maintaining inflammation and disease recurrence