P23 Epidermal feed-forward inflammatory loop in psoriasis plays a dominant role in psoriasis development

Abstract Skin is the outmost barrier that separates the human body from the external environment. In psoriasis, immune cells are resident and/or infiltrated into the epidermis in order to form the epidermal immunological microenvironment (EIME) and constitute a complex interaction with keratinocytes, together with nerve and microbiota influence. Our results have shown that psoriasis is mainly mediated by a specific inflammatory environment composed by keratinocyte-neuro-immune cell units (KNICUs), which is the interaction of activated epidermal immune cells, keratinocytes and peripheral nerve fibres, which are increased in psoriatic lesions and are closely innervated around immune cells and keratinocytes. We mapped psoriatic skin immune cells from a paired lesion, a perilesion, and a nonlesion using mass cytometry. Phenotypical dendritic cells (DCs) were found in the psoriatic epidermis and dermis. Psoriatic dermal CD1c+CD11b+ cDC2s migrated to the epidermis in the perilesional skin, positioned in preinitiation. CD1c+CD11b+ cDC2s rapidly replaced EpCAM+CD11clowLC cells and initiated inflammation. Simultaneously, CD207+CD11chiLC and CD5+ T cells occurred in the psoriatic epidermis and orchestrated epidermal inflammation in psoriasis. Multiple units gather to complete circulatory and amplified loop, both an epidermal feed-forward inflammatory loop constituted with epidermal dendritic cells pDC, cDC, Langerhans cells and CD8+T cells. The epidermal loop was more significant and coincided with the inflammation of psoriasis.