SOCS 是细胞因子、生长因子和激素诱导的分子级联的负抑制剂家族。在分子水平上，SOCS 蛋白抑制特定受体相关 Janus 激活激酶 (JAK) 组的激酶活性，从而抑制细胞内信号的传播。在八个已知成员中，SOCS1 和 SOCS3 抑制主要由细胞因子诱导的 JAK 活性，并在调节炎症和免疫反应中发挥关键作用。 SOCS1 和 SOCS3 是皮肤炎症性疾病中最有特色的 SOCS 成员，它们对细胞因子激活的 JAK 的抑制活性以及随之而来的抗炎作用已在表皮角质形成细胞中得到广泛研究。在结构上，SOCS1 和 SOCS3 共享一个包含激酶抑制区 (KIR) 基序的 N 端结构域，能够充当 JAK 的伪底物并抑制其活性。在过去的几十年中，在皮肤病实验模型中模拟 KIR 结构域的 SOCS1 和 SOCS3 衍生肽的设计和使用明确确立了 JAK 抑制对皮肤炎症反应的强大抗炎和改善作用。在此，我们讨论了过去收集的关于 SOCS1 和 SOCS3 在与皮肤免疫介导的疾病和恶性肿瘤相关的炎症反应中的功能的研究结果对于 JAK 抑制剂药物开发的重要性。其中，不同的 JAK 抑制剂已被引入临床实践，用于治疗特应性皮炎和牛皮癣，其他药物正在研究用于治疗斑秃和白癜风等皮肤病。版权所有 © 2024 Morelli、Madonna 和 Albanesi。

SOCS are a family of negative inhibitors of the molecular cascades induced by cytokines, growth factors and hormones. At molecular level, SOCS proteins inhibit the kinase activity of specific sets of receptor-associated Janus Activated Kinases (JAKs), thereby suppressing the propagation of intracellular signals. Of the eight known members, SOCS1 and SOCS3 inhibit activity of JAKs mainly induced by cytokines and can play key roles in regulation of inflammatory and immune responses. SOCS1 and SOCS3 are the most well-characterized SOCS members in skin inflammatory diseases, where their inhibitory activity on cytokine activated JAKs and consequent anti-inflammatory action has been widely investigated in epidermal keratinocytes. Structurally, SOCS1 and SOCS3 share the presence of a N-terminal domain containing a kinase inhibitory region (KIR) motif able to act as a pseudo-substrate for JAK and to inhibit its activity. During the last decades, the design and employment of SOCS1 and SOCS3-derived peptides mimicking KIR domains in experimental models of dermatoses definitively established a strong anti-inflammatory and ameliorative impact of JAK inhibition on skin inflammatory responses. Herein, we discuss the importance of the findings collected in the past on SOCS1 and SOCS3 function in the inflammatory responses associated to skin immune-mediated diseases and malignancies, for the development of the JAK inhibitor drugs. Among them, different JAK inhibitors have been introduced in the clinical practice for treatment of atopic dermatitis and psoriasis, and others are being investigated for skin diseases like alopecia areata and vitiligo.Copyright © 2024 Morelli, Madonna and Albanesi.