Abstract
BackgroundAlthough recent studies indicate a crucial role for IL-17A and IL-22 producing T cells in the pathogenesis of psoriasis, limited information is available on their frequency and heterogeneity and their distribution in skin in situ.Methodology/Principal FindingsBy spectral imaging analysis of double-stained skin sections we demonstrated that IL-17 was mainly expressed by mast cells and neutrophils and IL-22 by macrophages and dendritic cells. Only an occasional IL-17pos, but no IL-22pos T cell could be detected in psoriatic skin, whereas neither of these cytokines was expressed by T cells in normal skin. However, examination of in vitro-activated T cells by flow cytometry revealed that substantial percentages of skin-derived CD4 and CD8 T cells were able to produce IL-17A alone or together with IL-22 (i.e. Th17 and Tc17, respectively) or to produce IL-22 in absence of IL-17A and IFN-γ (i.e. Th22 and Tc22, respectively). Remarkably, a significant proportional rise in Tc17 and Tc22 cells, but not in Th17 and Th22 cells, was found in T cells isolated from psoriatic versus normal skin. Interestingly, we found IL-22 single-producers in many skin-derived IL-17Apos CD4 and CD8 T cell clones, suggesting that in vivo IL-22 single-producers may arise from IL-17Apos T cells as well.Conclusions/SignificanceThe increased presence of Tc17 and Tc22 cells in lesional psoriatic skin suggests that these types of CD8 T cells play a significant role in the pathogenesis of psoriasis. As part of the skin-derived IL-17Apos CD4 and CD8 T clones developed into IL-22 single-producers, this demonstrates plasticity in their cytokine production profile and suggests a developmental relationship between Th17 and Th22 cells and between Tc17 and Tc22 cells.
Highlights
Psoriasis is a chronic inflammatory skin disease of unknown etiology, characterized by T cell infiltrates and epidermal thickening, due to hyperproliferation of keratinocytes [1,2,3,4]
Whereas clear IL-17pos and CD3pos cells could be observed in lesional psoriatic skin (Figures 1A and 1B), only an occasional T cell appeared to co-express IL-17
Because recent experimental findings suggest an important role for IL-17A and IL-22 producing T cells in the pathogenesis of psoriasis, we focused in this study on these types of T cells and studied their relative proportion in the CD4 and CD8 skin resident T cell population in psoriatic skin and normal skin
Summary
Psoriasis is a chronic inflammatory skin disease of unknown etiology, characterized by T cell infiltrates and epidermal thickening, due to hyperproliferation of keratinocytes [1,2,3,4]. Psoriasis was considered to be a Th1-mediated disease, because of the relative increase of circulating and skinresiding IFN-c-producing T cells [5,6] and the activation of many IFN-c-induced immune response genes [7]. Levels of mRNA for the IL-23p19 and common IL-12/IL-23p40 units, but not for the IL-12p35 unit, are increased in lesional skin of psoriasis patients [13,15] and at protein level IL-23 is more abundantly expressed [16]. Recent studies indicate a crucial role for IL-17A and IL-22 producing T cells in the pathogenesis of psoriasis, limited information is available on their frequency and heterogeneity and their distribution in skin in situ
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