Keratinocyte hyperproliferation is a key pathogenic factor in psoriasis. However, the mechanisms that regulate keratinocyte hyperproliferation in this condition remain unclear. Here, we found that SLC35E1 was highly expressed in keratinocytes of patients with psoriasis and that Slc35e1^−/− mice displayed a less severe imiquimod (IMQ)-induced psoriasis-like phenotype than their wild-type siblings. In addition, SLC35E1 deficiency inhibited keratinocyte proliferation in both mice and cultured cells. On a molecular level, SLC35E1 was found to regulate zinc ion concentrations and subcellular localization, while zinc ion chelation reversed the IMQ-induced psoriatic phenotype in Slc35e1^−/− mice. Meanwhile, epidermal zinc ion levels were decreased in patients with psoriasis and zinc ion supplementation alleviated the psoriatic phenotype in an IMQ-induced mouse model of psoriasis. Our results indicated that SLC35E1 can promote keratinocyte proliferation by regulating zinc ion homeostasis and zinc ion supplementation has potential as a therapy for psoriasis.

角质形成细胞过度增殖是牛皮癣的关键致病因素。然而，在这种情况下调节角质形成细胞过度增殖的机制仍不清楚。在这里，我们发现SLC35E1在银屑病患者的角质形成细胞中高表达，并且Slc35e1 ^{- / -}小鼠表现出比其野生型同胞更不严重的咪喹莫特（IMQ）诱导的银屑病样表型。此外，SLC35E1 缺陷会抑制小鼠和培养细胞的角质形成细胞增殖。在分子水平上，SLC35E1被发现可以调节锌离子浓度和亚细胞定位，而锌离子螯合逆转了Slc35e1 ^{- / -}小鼠中IMQ诱导的银屑病表型。同时，银屑病患者的表皮锌离子水平降低，补充锌离子可减轻 IMQ 诱导的银屑病小鼠模型中的银屑病表型。我们的结果表明，SLC35E1 可以通过调节锌离子稳态来促进角质形成细胞增殖，补充锌离子具有治疗牛皮癣的潜力。