Abstract
Psoriasis is a chronic inflammatory skin disease characterized by abnormal keratinocyte proliferation and terminal differentiation. Interleukin-22 (IL-22) and the transcription factor Stat3 play pivotal roles in the pathogenesis of psoriasis. CD147 is a transmembrane glycosylation protein that belongs to the immunoglobulin superfamily. Our previous studies have shown that CD147 is a marker of high keratinocyte proliferation and poor keratinocyte differentiation as well as a psoriasis susceptibility gene. The current study demonstrates that CD147 is highly expressed in psoriatic skin lesions. Specific CD147 over-expression in the epidermis of K5-promoter transgenic mice promotes imiquimod (IMQ)-induced psoriasis-like inflammation characterized by acanthosis, granular layer loss and inflammatory cell infiltration. We also found that IL-22 increases CD147 transcription in vitro and in vivo and that Stat3 binds directly to the CD147 promoter between positions −854 and −440, suggesting that CD147 expression is up-regulated in patients with psoriasis through Stat3 activation. In addition, CD147 knockdown dramatically blocks IL-22-mediated Stat3 activation as well as IL-22-induced cytokine, chemokine and antimicrobial factor expression. Together, these findings show that CD147 is a novel and key mediator of IL-22-induced psoriatic alterations in the epidermis and might be a therapeutic target in patients with psoriasis.
Highlights
Psoriasis is an immune-mediated chronic inflammatory skin disease characterized by abnormal epidermal keratinocyte hyperplasia and differentiation as well as T cell, neutrophil and macrophage infiltration[1,2,3,4]
CD147 expression is clearly limited to the basal layer of the epidermis and does not occur in other layers (Fig. 1A,B), suggesting that CD147 plays a key role in initiating keratinocyte proliferation in psoriasis
These results demonstrate that CD147 expression is significantly increased in IMQ-treated mice and the skin lesions of patients with psoriasis, suggesting that CD147 expression in psoriatic epidermal cells is functionally involved in the pathogenesis of psoriasis
Summary
Psoriasis is an immune-mediated chronic inflammatory skin disease characterized by abnormal epidermal keratinocyte hyperplasia and differentiation as well as T cell, neutrophil and macrophage infiltration[1,2,3,4]. Psoriatic skin lesions are typically characterized by the redness, thickness and scaling induced by epidermal hyperproliferation and inflammation. These symptoms severely impair patient quality of life. Chemokines and growth factors can be strongly induced in the keratinocytes of psoriatic lesions, causing inflammation, epithelial hyperplasia and immune cell mobilization, resulting in chronic skin lesion formation[7,8]. CD147 is highly expressed in the PBMCs of patients with psoriasis[27]
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