Department of Dermatology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 833, Taiwan.
Department of Dermatology, Fooyin University Hospital, Pingtung 928, Taiwan.
Int J Mol Sci. 2022 Aug 12;23(16):9030. doi: 10.3390/ijms23169030.
Small-fiber neuropathy (SFN) is suggested to be involved in the pathogenesis of some types of autoimmune connective tissue diseases. SFN with a reduction in epidermal nerve fibers might affect sensory fibers and cause neuropathic symptoms, such as pruritus and pain, which are common in both dermatomyositis (DM) and cutaneous lupus erythematosus (CLE). Nerve growth factor (NGF) has been recognized as important in nociception by regulating epidermal nerve fiber density and sensitizing the peripheral nervous system. The present study aimed to investigate whether SFN was associated with the cutaneous manifestations of DM and CLE. We also investigated the relationship between SFN and axon guidance molecules, such as NGF, amphiregulin (AREG), and semaphorin (Sema3A) in DM and CLE. To explore the molecular signaling, interleukin (IL)-18 and IL-31, which have been implicated in the cutaneous manifestation and neuropathic symptoms in DM, were examined in keratinocytes. Our results revealed that intraepidermal nerve fiber density (IENFD) was unchanged in patients with DM, but significantly reduced in IENFD in patients with CLE compared with healthy control. Increased epidermal expression of NGF and decreased expression of Sema3A were demonstrated in patients with DM. Furthermore, IL-18 and IL-31 both induced the production of NGF from keratinocytes. Taken together, IL-18 and IL-31 mediated epidermal NGF expression might contribute to the cutaneous neuropathic symptoms in DM, while SFN might be important for CLE.
小纤维神经病 (SFN) 被认为与某些类型的自身免疫性结缔组织疾病的发病机制有关。表皮神经纤维减少的 SFN 可能会影响感觉纤维并引起神经病理性症状，如瘙痒和疼痛，这些症状在皮肌炎 (DM) 和红斑狼疮 (CLE) 中都很常见。神经生长因子 (NGF) 通过调节表皮神经纤维密度和敏化周围神经系统，被认为在伤害感受中很重要。本研究旨在探讨 SFN 是否与 DM 和 CLE 的皮肤表现有关。我们还研究了 SFN 与轴突导向分子（如 NGF、 Amphiregulin (AREG) 和 Sema3A）在 DM 和 CLE 中的关系。为了探索分子信号，我们研究了白细胞介素 (IL)-18 和 IL-31，它们与 DM 的皮肤表现和神经病理性症状有关，在角质形成细胞中进行了检查。我们的结果表明，DM 患者的表皮内神经纤维密度 (IENFD) 没有变化，但 CLE 患者的 IENFD 明显低于健康对照组。在 DM 患者中，NGF 的表皮表达增加，而 Sema3A 的表达减少。此外，IL-18 和 IL-31 均可诱导角质形成细胞产生 NGF。综上所述，IL-18 和 IL-31 介导的表皮 NGF 表达可能导致 DM 的皮肤神经病理性症状，而 SFN 可能对 CLE 很重要。
