Nuclear inhibitor of protein phosphatase 1 (NIPP1) is a ubiquitously expressed nuclear protein that regulates functions of protein serine/threonine phosphatase-1 in cell proliferation and lineage specification. The role of NIPP1 in tissue homeostasis is not fully understood. This study shows that the selective deletion of NIPP1 in mouse epidermis resulted in epidermal hyperproliferation, a reduced adherence of basal keratinocytes, and a gradual decrease in the stemness of hair follicle stem cells, culminating in hair loss. This complex phenotype was associated with chronic sterile skin inflammation and could be partially rescued by dexamethasone treatment. NIPP1-deficient keratinocytes massively expressed proinflammatory chemokines and immunomodulatory proteins in a cell-autonomous manner. Chemokines subsequently induced the recruitment and activation of immune cells, in particular conventional dendritic cells and Langerhans cells, accounting for the chronic inflammation phenotype. The data identifies NIPP1 as a key regulator of epidermal homeostasis and as a potential target for the treatment of inflammatory skin diseases.

蛋白磷酸酶 1 的核抑制剂 (NIPP1) 是一种普遍表达的核蛋白，可调节蛋白丝氨酸/苏氨酸磷酸酶-1 在细胞增殖和谱系规范中的功能。NIPP1 在组织稳态中的作用尚不完全清楚。该研究表明，小鼠表皮中 NIPP1 的选择性缺失导致表皮过度增殖，基底角质形成细胞的粘附减少，毛囊干细胞的干性逐渐降低，最终导致脱发。这种复杂的表型与慢性无菌性皮肤炎症有关，可以通过地塞米松治疗部分挽救。NIPP1 缺陷的角质形成细胞以细胞自主方式大量表达促炎趋化因子和免疫调节蛋白。趋化因子随后诱导免疫细胞的募集和激活，特别是常规树突状细胞和朗格汉斯细胞，解释了慢性炎症表型。数据表明 NIPP1 是表皮稳态的关键调节因子，也是治疗炎症性皮肤病的潜在靶点。