Fundación Valle del Lili, Centro de Investigaciones Clínicas, Cra 98 No. 18-49, Cali 760032, Colombia.
Southern Illinois University School of Medicine, Department of Medical Microbiology, Immunology and Cell Biology, Springfield, IL, USA.
Autoimmun Rev. 2023 Feb;22(2):103262. doi: 10.1016/j.autrev.2022.103262. Epub 2022 Dec 20.
Cutaneous lupus erythematosus (CLE) is a common disease that may appear as a separate entity from systemic lupus erythematosus (SLE), precede SLE development, or occur as a manifestation of this systemic disease. It has a complex pathophysiology that involves genetic, environmental, and immune-mediated factors creating a self-amplification pro-inflammatory cycle. CLE is characterized by prominent type I interferons (IFNs) inflammation which are considered as the first precursors of the inflammatory cascade generated within the pathophysiology of CLE. TNF-α enhances the production of antibodies through the activation of B cells, and favors the expression of surface nuclear antigens on keratinocytes. UV light exposure favors keratinocyte apoptosis or necroptosis, which results in the release of multiple proinflammatory cytokines, including IL-6, IL-1α, IL-1β, TNF-α, IFNs, and CXCL10. Serum levels of IL-17 are elevated in patients with ACLE, SCLE, and DLE. Evidence suggests IL-22 plays a role primarily in tissue repair rather than in inflammation. High expression of BAFF and its receptors have been found in lesioned keratinocytes of patients with CLE, and patients with CLE have lower serum levels of the regulatory cytokines TGF-β and IL-10. The chemokines CXCL9 and CXCL10 (CXCR3 ligands) have an increased expression among these patients, and their expression is correlated with IFNs levels. CXCR3 ligands recruit cytotoxic type I cells through this receptor, further supporting the death of keratinocytes via necroptosis with the subsequent release of eNAs perpetuating the inflammatory cycle. Interface dermatitis is characterized by the presence of CXCR3-positive lymphocytes. This review describes the leading cytokines and chemokines present in the circulation and skin that play a fundamental role in the pathogenesis of CLE.
皮肤红斑狼疮（CLE）是一种常见疾病，它可能与系统性红斑狼疮（SLE）是两种独立的疾病，也可能先于 SLE 发生，或者是系统性疾病的一种表现。它的发病机制复杂，涉及遗传、环境和免疫介导等多种因素，形成了一个自我放大的促炎循环。CLE 的特征是明显的 I 型干扰素（IFN）炎症，被认为是 CLE 病理生理学中炎症级联反应的第一个前体。TNF-α 通过激活 B 细胞来增强抗体的产生，并促进角质形成细胞表面核抗原的表达。紫外线照射有利于角质形成细胞凋亡或坏死，导致多种促炎细胞因子的释放，包括 IL-6、IL-1α、IL-1β、TNF-α、IFN 和 CXCL10。活动期盘状红斑狼疮（ACLE）、系统性红斑狼疮（SLE）和慢性光化性皮炎（DLE）患者的血清 IL-17 水平升高。有证据表明，IL-22 主要在组织修复中发挥作用，而不是在炎症中发挥作用。在 CLE 患者的皮损角质形成细胞中发现 BAFF 及其受体表达增加，且 CLE 患者的调节性细胞因子 TGF-β 和 IL-10 血清水平较低。趋化因子 CXCL9 和 CXCL10（CXCR3 配体）在这些患者中的表达增加，其表达与 IFN 水平相关。CXCR3 配体通过该受体招募细胞毒性 I 型细胞，进一步通过坏死导致角质形成细胞死亡，随后释放 eNAs 使炎症循环持续。界面性皮炎的特征是存在 CXCR3 阳性淋巴细胞。本文综述了在循环和皮肤中发挥重要作用的促炎细胞因子和趋化因子在 CLE 发病机制中的作用。
