Immunology Research Center for Oral and Systemic Health, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, China.
Medical Research Center, Beijing Institute of Respiratory Medicine and Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China.
J Transl Med. 2024 Apr 2;22(1):328. doi: 10.1186/s12967-024-05132-8.
Psoriasis is a chronic immune-mediated skin condition. Although biologic treatments are effective in controlling psoriasis, some patients do not respond or lose response to these therapies. Thus, new strategies for psoriasis treatment are still urgently needed. Double-negative T cells (DNT) play a significant immunoregulatory role in autoimmune diseases. In this study, we aimed to evaluate the protective effect of DNT in psoriasis and explore the underlying mechanism.
We conducted a single adoptive transfer of DNT into an imiquimod (IMQ)-induced psoriasis mouse model through tail vein injection. The skin inflammation and IL-17A producing γδ T cells were evaluated.
DNT administration significantly reduced the inflammatory response in mouse skin, characterized by decreased skin folds, scales, and red patches. After DNT treatment, the secretion of IL-17A by RORc γδ T cells in the skin was selectively suppressed, resulting in an amelioration of skin inflammation. Transcriptomic data suggested heightened expression of NKG2D ligands in γδ T cells within the mouse model of psoriasis induced by IMQ. When blocking the NKG2D ligand and NKG2D (expressed by DNT) interaction, the cytotoxic efficacy of DNT against RORcIL17A γδ T cells was attenuated. Using Ccr5 DNT for treatment yielded evidence that DNT migrates into inflamed skin tissue and fails to protect IMQ-induced skin lesions.
DNT could migrate to inflamed skin tissue through CCR5, selectively inhibit IL-17-producing γδ T cells and finally ameliorate mouse psoriasis. Our study provides feasibility for using immune cell therapy for the prevention and treatment of psoriasis in the clinic.
银屑病是一种慢性免疫介导的皮肤疾病。虽然生物制剂在控制银屑病方面非常有效，但有些患者对这些治疗方法没有反应或失去反应。因此，仍然迫切需要新的银屑病治疗策略。双阴性 T 细胞（DNT）在自身免疫性疾病中发挥重要的免疫调节作用。在本研究中，我们旨在评估 DNT 在银屑病中的保护作用，并探讨其潜在机制。
我们通过尾静脉注射将 DNT 单次过继转移到咪喹莫特（IMQ）诱导的银屑病小鼠模型中。评估皮肤炎症和产生 IL-17A 的 γδ T 细胞。
DNT 给药显著减轻了小鼠皮肤的炎症反应，表现为皮肤褶皱、鳞屑和红斑减少。在 DNT 治疗后，皮肤中 RORc γδ T 细胞分泌的 IL-17A 被选择性抑制，从而改善了皮肤炎症。转录组数据表明，在 IMQ 诱导的银屑病小鼠模型中，γδ T 细胞中 NKG2D 配体的表达水平升高。当阻断 NKG2D 配体和 NKG2D（由 DNT 表达）的相互作用时，DNT 对 RORcIL17A γδ T 细胞的细胞毒性作用会减弱。使用 Ccr5 DNT 进行治疗的结果表明，DNT 可以通过 CCR5 迁移到炎症皮肤组织中，无法保护 IMQ 诱导的皮肤损伤。
DNT 可以通过 CCR5 迁移到炎症皮肤组织中，选择性地抑制产生 IL-17A 的 γδ T 细胞，最终改善小鼠银屑病。我们的研究为使用免疫细胞疗法预防和治疗银屑病提供了临床可行性。
